Roger Hainsworth | University of Leeds (original) (raw)
Papers by Roger Hainsworth
Genome biology, 2014
Although it has long been proposed that genetic factors contribute to adaptation to high altitude... more Although it has long been proposed that genetic factors contribute to adaptation to high altitude, such factors remain largely unverified. Recent advances in high-throughput sequencing have made it feasible to analyze genome-wide patterns of genetic variation in human populations. Since traditionally such studies surveyed only a small fraction of the genome, interpretation of the results was limited. We report here the results of the first whole genome resequencing-based analysis identifying genes that likely modulate high altitude adaptation in native Ethiopians residing at 3,500 m above sea level on Bale Plateau or Chennek field in Ethiopia. Using cross-population tests of selection, we identify regions with a significant loss of diversity, indicative of a selective sweep. We focus on a 208 kbp gene-rich region on chromosome 19, which is significant in both of the Ethiopian subpopulations sampled. This region contains eight protein-coding genes and spans 135 SNPs. To elucidate its...
The Journal of Physiology
Many previous studies claimed that stimulation of left ventricular mechanoreceptors induce powerf... more Many previous studies claimed that stimulation of left ventricular mechanoreceptors induce powerful depressor responses (Hainsworth, 1991). However, reports from our laboratory have indicated that the major reflexogenic area may lie in the coronary arteries rather than the ventricle (Al-Timman et al., 1993; Drinkhill et al., 1993). The aims of this study were to examine the reflex vascular responses to discrete stimulation of the two reflexogenic areas and, secondarily, to study the sensitivity of the ventricular reflexes to changes in end-diastolic and systolic ventricular pressures. All experiments were carried out in chloralose anaesthetised dogs (100 mg / kg i.v. in saline). A cannula inserted in the aortic root controlled the coronary arterial pressure and a balloon at the aortic valve separated the pressure stimuli to coronary and ventricular receptors. Ventricular end-diastolic and systolic pressures were controlled by the rate at which blood was pumped in through an apical c...
The left ventricle is richly innervated by non-myelinated nerves1 which can be excited by mechani... more The left ventricle is richly innervated by non-myelinated nerves1 which can be excited by mechanical or chemical stimuli or both.2 However, because of the difficulty in applying discrete stimuli to these nerves, there have been no studies which have compared the reflex responses to chemical and mechanical stimuli in the same animals. In this study we compared the responses to injection of chemical stimulants into the coronary arteries with those to changes in ventricular pressures. Dogs were anaesthetised with chloralose (100 mg / kg i.v.) and artificially ventilated. A cannula inserted in the aortic root controlled coronary perfusion pressure, whilst a pig-tail balloon catheter was positioned to occlude the aortic valve and isolate the left ventricle from the coronary circulation. End-diastolic pressure was changed by changing ventricular inflow and pressure applied to a Starling resistor controlled ventricular outflow and thus systolic pressure. Veratridine (30-60 µg) was injected...
The Physiologist
It is widely accepted that stimulation of left ventricular receptors induces powerful vasodepress... more It is widely accepted that stimulation of left ventricular receptors induces powerful vasodepressor responses (Hainsworth, 1991). While there is no doubt that stimulation of chemosensitive afferents is effective, the evidence for major responses from mechanosensitive nerves is much less secure. The reason for the uncertainty is that most previous studies of responses to the stimulation of ventricular mechanosensitive nerves would also have changed the stimulus to mechanoreceptors in the coronary circulation (Drinkhill et al., 1993). In α-chloralose anaesthetized beagle dogs, the chest was opened and a cardiopulmonary bypass connected. A cannula tied in the ascending aorta allowed control of coronary artery pressure, and a balloon tied at the aortic valve separated coronary from ventricular pressures. Ventricular pressure was changed by applying various pressures to a cannula inserted into the ventricle through its apex. Pressures distending aortic and carotid baroreceptors were also...
Survey of Anesthesiology, 1985
Experimental physiology, 1998
The abdominal circulation contains a high proportion of the total blood volume and this can chang... more The abdominal circulation contains a high proportion of the total blood volume and this can change either passively in response to changes in vascular distending pressure or actively (termed a capacitance response) to changes in sympathetic nervous activity. The liver is the largest abdominal organ and this study was designed to evaluate its potential contribution to overall vascular capacitance and compliance. In chloralose anaesthetized dogs, the liver was vascularly isolated, perfused through the portal vein and hepatic artery at either constant pressures or constant flows and drained from the hepatic veins at constant pressure. Changes in vascular resistance were assessed from changes in inflow pressures or flows and hepatic blood volume was determined by differences between net inflow and outflow. During constant flow perfusion the change in hepatic volume (capacitance change) in response to supramaximal stimulation of sympathetic nerves at 16 Hz was (mean +/- S.E.M.) -2.40 +/-...
Experimental physiology, 1996
In chloralose-anaesthetized dogs, pressure applied to coronary, carotid and aortic baroreceptors ... more In chloralose-anaesthetized dogs, pressure applied to coronary, carotid and aortic baroreceptors were changed independently and the resulting reflex vascular responses were determined. Increases in pressure to each group of baroreceptors resulted in reflex vasodilatation; the maximal responses to distension of carotid and coronary baroreceptors were significantly larger than those to aortic receptors, but not different from each other. Increases in pressure in all three regions induced maximal responses at similar times from the onset of the pressure stimulus. However, the time for recovery of vascular resistance following a decrease in baroreceptor pressure differed. Vasoconstriction following a period of coronary hypertension occurred slowly, requiring 70 s for 90% of the response to develop. This was significantly longer than the corresponding times for carotid and aortic receptors (about 28 s). The rate of vasoconstriction in response to coronary baroreceptor unloading was influ...
British journal of pharmacology, 1973
During histamine infusion in the same four dogs, propranolol had no effect on the secretory plate... more During histamine infusion in the same four dogs, propranolol had no effect on the secretory plateau and negligible effect on gastric mucosal blood flow. In another experiment on one of these dogs histamine-induced secretion increased during propranolol administration.
Quarterly journal of experimental physiology (Cambridge, England), 1987
In dogs anaesthetized with chloralose, cardiac receptors were stimulated by increases in left ven... more In dogs anaesthetized with chloralose, cardiac receptors were stimulated by increases in left ventricular systolic pressure effected by changes in aortic root pressure. Left atrial and carotid sinus pressures were controlled. A large step increase in ventricular pressure resulted in transient decreases in heart rate, systemic arterial perfusion pressure and perfusion pressure to a vascularly isolated hind limb. The magnitudes of these responses were about three-quarters of those to either a large change in carotid sinus pressure or aortic root injection of 20 micrograms veratridine. Steady-state responses were smaller. There was no significant change in perfusion pressure to a perfused cutaneous vein. Graded changes in ventricular systolic pressure showed that the most sensitive pressure range was between 20 and 24 kPa. These results indicate that changes in left ventricular pressure result in significant vasodilation in the hind limb and in other regions and that responses are obta...
Quarterly journal of experimental physiology (Cambridge, England), 1989
This study was undertaken to determine whether moderate increases in left ventricular systolic pr... more This study was undertaken to determine whether moderate increases in left ventricular systolic pressure in anaesthetized dogs result in changes in respiratory activity. Left ventricular systolic pressure was changed using a preparation in which the applied pressure did not distend the aortic arch and in which left atrial and carotid sinus pressures were held constant. The systemic circulation was perfused at constant flow and respiratory activity was assessed from the phrenic electroneurogram. Increases in aortic root and left ventricular systolic pressures resulted in a decrease in arterial perfusion pressure, no significant change in heart rate and a decrease in phrenic nerve activity. These responses differed from those to changes in carotid sinus pressure, which were decreases in perfusion pressure and heart rate but no significant steady-state change in phrenic activity. Responses to changes in ventricular pressure were obtained to each small step between 16 and 28 kPa (120 and...
The Journal of physiology, 1977
The Journal of physiology, 1979
The Journal of extra-corporeal technology, 2005
Previous studies have identified the presence of coronary baroreceptors in animal models. We set ... more Previous studies have identified the presence of coronary baroreceptors in animal models. We set up a study to explore the presence of coronary baroreceptors in humans, which was performed with isolated, graded aortic root perfusion in patients during cardiopulmonary bypass. With ethical approval 12 patients with normal coronary arteries, aged 58-75 (mean 69) years undergoing mitral valve surgery were recruited to the study with informed consent. Those with aortic valve incompetence, coronary, or peripheral artery disease and diabetes mellitus were excluded. They were randomized to have their coronary perfusion pressure set low at 50 mmHg for 90 seconds and then adjusted high to 80 mmHg for 90 seconds (group L-H) or the reverse sequence (group H-L). Average arterial pressure and approximately constant systemic flow over 30-second periods were used to calculate vascular resistance (SVR). The first six experiments followed initiation of cardiopulmonary bypass and aortic clamping but b...
American journal of hypertension, 2003
Previous work has established that a high dietary salt intake results in enhanced arterial vasoco... more Previous work has established that a high dietary salt intake results in enhanced arterial vasoconstrictor responses to stimulation with agonists. This investigation was designed to investigate the effects of dietary salt on the responses of isolated capacitance vessels (third order mesenteric veins). Dogs were fed diets containing low, intermediate, and high levels of dietary salt (0.4, 3.0, and 6.0 mmol kg/day). The animals were killed, and lengths of mesenteric vein were mounted in a perfusion myograph with changes in lumenal diameter measured using a video tracking device. Responses to cumulative doses of norepinephrine (NE) and acetylcholine (Ach) were then determined. The vasoconstrictor responses to NE were greater in the veins from dogs on a high salt diet. Acetylcholine also caused venoconstriction that also was greater in the high salt group of animals. Responses to Ach were unaffected by N(omega)-nitro-L-arginine methyl ester but were abolished by atropine. These results ...
Clinical science (London, England : 1979), 2002
During orthostatic stress, an increase in peripheral vascular resistance normally results in arte... more During orthostatic stress, an increase in peripheral vascular resistance normally results in arterial blood pressure being well maintained, despite a decrease in cardiac output. The present study was undertaken to determine whether the sensitivity of the carotid baroreceptor reflex was increased during orthostatic stress and whether failure to develop this increase was associated with poor orthostatic tolerance. Three groups of subjects were studied: asymptomatic controls; patients investigated for suspected posturally related syncope but who had normal responses to an orthostatic stress test (normal patients); and patients who were shown to have low orthostatic tolerance (early fainters). We determined responses of R-R interval and forearm vascular resistance (mean arterial pressure/brachial artery velocity by Doppler ultrasonography) to the loading and unloading of carotid baroreceptors by application of pressures of -30 and +30 mmHg to a chamber fitted over the neck. Responses we...
The Journal of physiology, Jan 15, 2002
A high salt diet in some species results in elevated arterial blood pressure and alterations in v... more A high salt diet in some species results in elevated arterial blood pressure and alterations in vascular smooth muscle responses to agonists. Weanling male Sprague-Dawley rats were given either a high salt diet containing 8 % or a low salt diet of 0.4 % sodium chloride for a period of 4 weeks. At the end of the feeding period, tail systolic pressure was higher in the high salt than in low salt rats. The rats were then killed and the intestines removed. Vascular smooth muscle (VSM) responses were estimated from the changes in lumenal diameter of pressurised second order mesenteric resistance arteries. High salt diet resulted in enhanced VSM responses to noradrenaline. The vessels dilated in response both to acetylcholine and to sodium nitroprusside and the responses were similar in vessels from both high and low salt rats. However, vessels from high salt rats were resistant to the blocking of endothelium derived nitric oxide (EDNO) with L-NAME and the responses were instead abolished...
Experimental physiology, 1999
The effect of physical training on an individual's ability to withstand an orthostatic stress... more The effect of physical training on an individual's ability to withstand an orthostatic stress is unclear. This study was undertaken to determine the effects on orthostatic tolerance in healthy volunteers of training at a level appropriate for unfit subjects and cardiorespiratory patients. In 11 asymptomatic, untrained subjects the following assessments were made: plasma volume by Evans Blue dye dilution and blood volume derived from haematocrit; carotid baroreceptor sensitivity from the slope of the regression of change in cardiac interval against pressure applied to a neck chamber; orthostatic tolerance as time to presyncope in a test of head-up tilting combined with lower body suction; exercise test relating heart rate to oxygen consumption. Subjects were then given a training schedule (5BX/XBX, Royal Canadian Air Force) involving 11-12 min of mixed exercises per day until an age/sex related 'target' was reached. Following training all subjects showed evidence of impro...
Heart (British Cardiac Society), 1998
To determine whether a programme of simple, moderate exercise training increases blood volume and... more To determine whether a programme of simple, moderate exercise training increases blood volume and improves orthostatic tolerance in patients with attacks of syncope or near syncope related to orthostatic stress. An open study in 14 patients referred with unexplained attacks of syncope, who were shown to have a low tolerance to an orthostatic stress test. Measurements were made of plasma and blood volumes, orthostatic tolerance to a test of combined head up tilt and lower body suction, and baroreceptor sensitivity by applying subatmospheric pressures to a chamber over the neck. Cardiorespiratory fitness was assessed from the relation between heart rate and oxygen uptake during a graded treadmill exercise test. Assessments were made before and after undertaking an exercise training programme (Canadian Air Force 5BX/XBX). After the training period, 12 of the 14 patients showed evidence of improved cardiorespiratory fitness. All 12 patients were symptomatically improved; they showed inc...
The American journal of physiology, 1998
This study examined reflex vascular responses to large rapid increases and decreases in carotid s... more This study examined reflex vascular responses to large rapid increases and decreases in carotid sinus pressure to determine whether delayed or inappropriate vascular responses might be obtained that, if they occurred in people, could lead to hypotension during exposure to rapidly alternating gravitational forces. In chloralose-anesthetized open-chest dogs, a perfusion circuit controlled carotid sinus and thoracic aortic pressures and blood flows to both the vascularly isolated abdominal circulation and a hindlimb (perfusion pressure changes denoted resistance). When carotid pressure was increased and decreased over the range of 60-180 mmHg, the resulting reflex vasodilatation occurred significantly more rapidly than the vasoconstriction (P < 0.001). In the abdominal vascular bed, time constants for vasodilatation and vasoconstriction were 4.2 +/- 0.5 and 7.5 +/- 1.0 s, respectively. Decreases in carotid pressure in pulses of 10-s duration or less failed to elicit maximal vasocons...
Genome biology, 2014
Although it has long been proposed that genetic factors contribute to adaptation to high altitude... more Although it has long been proposed that genetic factors contribute to adaptation to high altitude, such factors remain largely unverified. Recent advances in high-throughput sequencing have made it feasible to analyze genome-wide patterns of genetic variation in human populations. Since traditionally such studies surveyed only a small fraction of the genome, interpretation of the results was limited. We report here the results of the first whole genome resequencing-based analysis identifying genes that likely modulate high altitude adaptation in native Ethiopians residing at 3,500 m above sea level on Bale Plateau or Chennek field in Ethiopia. Using cross-population tests of selection, we identify regions with a significant loss of diversity, indicative of a selective sweep. We focus on a 208 kbp gene-rich region on chromosome 19, which is significant in both of the Ethiopian subpopulations sampled. This region contains eight protein-coding genes and spans 135 SNPs. To elucidate its...
The Journal of Physiology
Many previous studies claimed that stimulation of left ventricular mechanoreceptors induce powerf... more Many previous studies claimed that stimulation of left ventricular mechanoreceptors induce powerful depressor responses (Hainsworth, 1991). However, reports from our laboratory have indicated that the major reflexogenic area may lie in the coronary arteries rather than the ventricle (Al-Timman et al., 1993; Drinkhill et al., 1993). The aims of this study were to examine the reflex vascular responses to discrete stimulation of the two reflexogenic areas and, secondarily, to study the sensitivity of the ventricular reflexes to changes in end-diastolic and systolic ventricular pressures. All experiments were carried out in chloralose anaesthetised dogs (100 mg / kg i.v. in saline). A cannula inserted in the aortic root controlled the coronary arterial pressure and a balloon at the aortic valve separated the pressure stimuli to coronary and ventricular receptors. Ventricular end-diastolic and systolic pressures were controlled by the rate at which blood was pumped in through an apical c...
The left ventricle is richly innervated by non-myelinated nerves1 which can be excited by mechani... more The left ventricle is richly innervated by non-myelinated nerves1 which can be excited by mechanical or chemical stimuli or both.2 However, because of the difficulty in applying discrete stimuli to these nerves, there have been no studies which have compared the reflex responses to chemical and mechanical stimuli in the same animals. In this study we compared the responses to injection of chemical stimulants into the coronary arteries with those to changes in ventricular pressures. Dogs were anaesthetised with chloralose (100 mg / kg i.v.) and artificially ventilated. A cannula inserted in the aortic root controlled coronary perfusion pressure, whilst a pig-tail balloon catheter was positioned to occlude the aortic valve and isolate the left ventricle from the coronary circulation. End-diastolic pressure was changed by changing ventricular inflow and pressure applied to a Starling resistor controlled ventricular outflow and thus systolic pressure. Veratridine (30-60 µg) was injected...
The Physiologist
It is widely accepted that stimulation of left ventricular receptors induces powerful vasodepress... more It is widely accepted that stimulation of left ventricular receptors induces powerful vasodepressor responses (Hainsworth, 1991). While there is no doubt that stimulation of chemosensitive afferents is effective, the evidence for major responses from mechanosensitive nerves is much less secure. The reason for the uncertainty is that most previous studies of responses to the stimulation of ventricular mechanosensitive nerves would also have changed the stimulus to mechanoreceptors in the coronary circulation (Drinkhill et al., 1993). In α-chloralose anaesthetized beagle dogs, the chest was opened and a cardiopulmonary bypass connected. A cannula tied in the ascending aorta allowed control of coronary artery pressure, and a balloon tied at the aortic valve separated coronary from ventricular pressures. Ventricular pressure was changed by applying various pressures to a cannula inserted into the ventricle through its apex. Pressures distending aortic and carotid baroreceptors were also...
Survey of Anesthesiology, 1985
Experimental physiology, 1998
The abdominal circulation contains a high proportion of the total blood volume and this can chang... more The abdominal circulation contains a high proportion of the total blood volume and this can change either passively in response to changes in vascular distending pressure or actively (termed a capacitance response) to changes in sympathetic nervous activity. The liver is the largest abdominal organ and this study was designed to evaluate its potential contribution to overall vascular capacitance and compliance. In chloralose anaesthetized dogs, the liver was vascularly isolated, perfused through the portal vein and hepatic artery at either constant pressures or constant flows and drained from the hepatic veins at constant pressure. Changes in vascular resistance were assessed from changes in inflow pressures or flows and hepatic blood volume was determined by differences between net inflow and outflow. During constant flow perfusion the change in hepatic volume (capacitance change) in response to supramaximal stimulation of sympathetic nerves at 16 Hz was (mean +/- S.E.M.) -2.40 +/-...
Experimental physiology, 1996
In chloralose-anaesthetized dogs, pressure applied to coronary, carotid and aortic baroreceptors ... more In chloralose-anaesthetized dogs, pressure applied to coronary, carotid and aortic baroreceptors were changed independently and the resulting reflex vascular responses were determined. Increases in pressure to each group of baroreceptors resulted in reflex vasodilatation; the maximal responses to distension of carotid and coronary baroreceptors were significantly larger than those to aortic receptors, but not different from each other. Increases in pressure in all three regions induced maximal responses at similar times from the onset of the pressure stimulus. However, the time for recovery of vascular resistance following a decrease in baroreceptor pressure differed. Vasoconstriction following a period of coronary hypertension occurred slowly, requiring 70 s for 90% of the response to develop. This was significantly longer than the corresponding times for carotid and aortic receptors (about 28 s). The rate of vasoconstriction in response to coronary baroreceptor unloading was influ...
British journal of pharmacology, 1973
During histamine infusion in the same four dogs, propranolol had no effect on the secretory plate... more During histamine infusion in the same four dogs, propranolol had no effect on the secretory plateau and negligible effect on gastric mucosal blood flow. In another experiment on one of these dogs histamine-induced secretion increased during propranolol administration.
Quarterly journal of experimental physiology (Cambridge, England), 1987
In dogs anaesthetized with chloralose, cardiac receptors were stimulated by increases in left ven... more In dogs anaesthetized with chloralose, cardiac receptors were stimulated by increases in left ventricular systolic pressure effected by changes in aortic root pressure. Left atrial and carotid sinus pressures were controlled. A large step increase in ventricular pressure resulted in transient decreases in heart rate, systemic arterial perfusion pressure and perfusion pressure to a vascularly isolated hind limb. The magnitudes of these responses were about three-quarters of those to either a large change in carotid sinus pressure or aortic root injection of 20 micrograms veratridine. Steady-state responses were smaller. There was no significant change in perfusion pressure to a perfused cutaneous vein. Graded changes in ventricular systolic pressure showed that the most sensitive pressure range was between 20 and 24 kPa. These results indicate that changes in left ventricular pressure result in significant vasodilation in the hind limb and in other regions and that responses are obta...
Quarterly journal of experimental physiology (Cambridge, England), 1989
This study was undertaken to determine whether moderate increases in left ventricular systolic pr... more This study was undertaken to determine whether moderate increases in left ventricular systolic pressure in anaesthetized dogs result in changes in respiratory activity. Left ventricular systolic pressure was changed using a preparation in which the applied pressure did not distend the aortic arch and in which left atrial and carotid sinus pressures were held constant. The systemic circulation was perfused at constant flow and respiratory activity was assessed from the phrenic electroneurogram. Increases in aortic root and left ventricular systolic pressures resulted in a decrease in arterial perfusion pressure, no significant change in heart rate and a decrease in phrenic nerve activity. These responses differed from those to changes in carotid sinus pressure, which were decreases in perfusion pressure and heart rate but no significant steady-state change in phrenic activity. Responses to changes in ventricular pressure were obtained to each small step between 16 and 28 kPa (120 and...
The Journal of physiology, 1977
The Journal of physiology, 1979
The Journal of extra-corporeal technology, 2005
Previous studies have identified the presence of coronary baroreceptors in animal models. We set ... more Previous studies have identified the presence of coronary baroreceptors in animal models. We set up a study to explore the presence of coronary baroreceptors in humans, which was performed with isolated, graded aortic root perfusion in patients during cardiopulmonary bypass. With ethical approval 12 patients with normal coronary arteries, aged 58-75 (mean 69) years undergoing mitral valve surgery were recruited to the study with informed consent. Those with aortic valve incompetence, coronary, or peripheral artery disease and diabetes mellitus were excluded. They were randomized to have their coronary perfusion pressure set low at 50 mmHg for 90 seconds and then adjusted high to 80 mmHg for 90 seconds (group L-H) or the reverse sequence (group H-L). Average arterial pressure and approximately constant systemic flow over 30-second periods were used to calculate vascular resistance (SVR). The first six experiments followed initiation of cardiopulmonary bypass and aortic clamping but b...
American journal of hypertension, 2003
Previous work has established that a high dietary salt intake results in enhanced arterial vasoco... more Previous work has established that a high dietary salt intake results in enhanced arterial vasoconstrictor responses to stimulation with agonists. This investigation was designed to investigate the effects of dietary salt on the responses of isolated capacitance vessels (third order mesenteric veins). Dogs were fed diets containing low, intermediate, and high levels of dietary salt (0.4, 3.0, and 6.0 mmol kg/day). The animals were killed, and lengths of mesenteric vein were mounted in a perfusion myograph with changes in lumenal diameter measured using a video tracking device. Responses to cumulative doses of norepinephrine (NE) and acetylcholine (Ach) were then determined. The vasoconstrictor responses to NE were greater in the veins from dogs on a high salt diet. Acetylcholine also caused venoconstriction that also was greater in the high salt group of animals. Responses to Ach were unaffected by N(omega)-nitro-L-arginine methyl ester but were abolished by atropine. These results ...
Clinical science (London, England : 1979), 2002
During orthostatic stress, an increase in peripheral vascular resistance normally results in arte... more During orthostatic stress, an increase in peripheral vascular resistance normally results in arterial blood pressure being well maintained, despite a decrease in cardiac output. The present study was undertaken to determine whether the sensitivity of the carotid baroreceptor reflex was increased during orthostatic stress and whether failure to develop this increase was associated with poor orthostatic tolerance. Three groups of subjects were studied: asymptomatic controls; patients investigated for suspected posturally related syncope but who had normal responses to an orthostatic stress test (normal patients); and patients who were shown to have low orthostatic tolerance (early fainters). We determined responses of R-R interval and forearm vascular resistance (mean arterial pressure/brachial artery velocity by Doppler ultrasonography) to the loading and unloading of carotid baroreceptors by application of pressures of -30 and +30 mmHg to a chamber fitted over the neck. Responses we...
The Journal of physiology, Jan 15, 2002
A high salt diet in some species results in elevated arterial blood pressure and alterations in v... more A high salt diet in some species results in elevated arterial blood pressure and alterations in vascular smooth muscle responses to agonists. Weanling male Sprague-Dawley rats were given either a high salt diet containing 8 % or a low salt diet of 0.4 % sodium chloride for a period of 4 weeks. At the end of the feeding period, tail systolic pressure was higher in the high salt than in low salt rats. The rats were then killed and the intestines removed. Vascular smooth muscle (VSM) responses were estimated from the changes in lumenal diameter of pressurised second order mesenteric resistance arteries. High salt diet resulted in enhanced VSM responses to noradrenaline. The vessels dilated in response both to acetylcholine and to sodium nitroprusside and the responses were similar in vessels from both high and low salt rats. However, vessels from high salt rats were resistant to the blocking of endothelium derived nitric oxide (EDNO) with L-NAME and the responses were instead abolished...
Experimental physiology, 1999
The effect of physical training on an individual's ability to withstand an orthostatic stress... more The effect of physical training on an individual's ability to withstand an orthostatic stress is unclear. This study was undertaken to determine the effects on orthostatic tolerance in healthy volunteers of training at a level appropriate for unfit subjects and cardiorespiratory patients. In 11 asymptomatic, untrained subjects the following assessments were made: plasma volume by Evans Blue dye dilution and blood volume derived from haematocrit; carotid baroreceptor sensitivity from the slope of the regression of change in cardiac interval against pressure applied to a neck chamber; orthostatic tolerance as time to presyncope in a test of head-up tilting combined with lower body suction; exercise test relating heart rate to oxygen consumption. Subjects were then given a training schedule (5BX/XBX, Royal Canadian Air Force) involving 11-12 min of mixed exercises per day until an age/sex related 'target' was reached. Following training all subjects showed evidence of impro...
Heart (British Cardiac Society), 1998
To determine whether a programme of simple, moderate exercise training increases blood volume and... more To determine whether a programme of simple, moderate exercise training increases blood volume and improves orthostatic tolerance in patients with attacks of syncope or near syncope related to orthostatic stress. An open study in 14 patients referred with unexplained attacks of syncope, who were shown to have a low tolerance to an orthostatic stress test. Measurements were made of plasma and blood volumes, orthostatic tolerance to a test of combined head up tilt and lower body suction, and baroreceptor sensitivity by applying subatmospheric pressures to a chamber over the neck. Cardiorespiratory fitness was assessed from the relation between heart rate and oxygen uptake during a graded treadmill exercise test. Assessments were made before and after undertaking an exercise training programme (Canadian Air Force 5BX/XBX). After the training period, 12 of the 14 patients showed evidence of improved cardiorespiratory fitness. All 12 patients were symptomatically improved; they showed inc...
The American journal of physiology, 1998
This study examined reflex vascular responses to large rapid increases and decreases in carotid s... more This study examined reflex vascular responses to large rapid increases and decreases in carotid sinus pressure to determine whether delayed or inappropriate vascular responses might be obtained that, if they occurred in people, could lead to hypotension during exposure to rapidly alternating gravitational forces. In chloralose-anesthetized open-chest dogs, a perfusion circuit controlled carotid sinus and thoracic aortic pressures and blood flows to both the vascularly isolated abdominal circulation and a hindlimb (perfusion pressure changes denoted resistance). When carotid pressure was increased and decreased over the range of 60-180 mmHg, the resulting reflex vasodilatation occurred significantly more rapidly than the vasoconstriction (P < 0.001). In the abdominal vascular bed, time constants for vasodilatation and vasoconstriction were 4.2 +/- 0.5 and 7.5 +/- 1.0 s, respectively. Decreases in carotid pressure in pulses of 10-s duration or less failed to elicit maximal vasocons...