AT1 Receptors in the RVLM Mediate Pressor Responses to Emotional Stress in Rabbits (original) (raw)
Related papers
Hypertension, 2004
Superoxide has been shown to be an important intracellular mediator of actions of angiotensin II. Recently, we found that blockade of angiotensin II type-1 receptors in the rostral ventrolateral medulla (RVLM) abrogated the pressor effect of emotional stress in rabbits. In the present study, we examined the influence of superoxide dismutase mimetics, tempol and tiron, in RVLM on cardiovascular stress response in conscious rabbits. Air-jet stress evoked a sustained increase in blood pressure (ϩ14Ϯ2 mm Hg), tachycardia (ϩ52Ϯ7 bpm), and renal sympathoactivation (ϩ58Ϯ8%). Bilateral microinjections of tempol or tiron (20 nmol) into RVLM did not alter resting cardiovascular parameters, but attenuated the pressor, sympathetic, and tachycardiac response to stress by 40% to 55%. By contrast, 3-carbamoylproxyl, which is structurally close to tempol but has a lower superoxide scavenging activity, did not alter the stress response. Neither tempol nor tiron altered the sympathoexcitatory response to glutamate microinjections into RVLM or to baroreceptor unloading. Microinjections of nitric oxide synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME; 10 nmol) into RVLM did not affect the stress response. Coinjections of tempol and L-NAME decreased the pressor response to stress by 35Ϯ3%. Tempol attenuated the pressor response to microinjection of angiotensin II into RVLM by 59Ϯ15%, whereas L-NAME did not alter this response. These results suggest that superoxide dismutase mimetics in RVLM attenuate, partially via a nitric oxide-independent mechanism, the pressor effect of emotional stress in rabbits. Together with our previous studies, these results also indicate that superoxide is a key mediator of excitatory actions of angiotensin II in RVLM during acute stress. (Hypertension. 2004;44:101-106.)
Baroreflex control of renal sympathetic nerve activity during air-jet stress in rats
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2006
The effects of acute emotional stress on the sympathetic component of the arterial baroreceptor reflex have not yet been described in conscious animals and humans. Arterial pressure (AP) and renal sympathetic nerve activity (RSNA) were simultaneously recorded in 11 conscious rats before and during exposure to a mild environmental stressor (jet of air). Baroreflex function curves relating AP and RSNA were constructed by fitting a sigmoid function to RSNA and AP measured during sequential nitroprusside and phenylephrine administrations. Stress increased mean AP from 112 ± 2 to 124 ± 2 mmHg, heart rate from 381 ± 10 to 438 ± 18 beats/min, and RSNA from 0.80 ± 0.14 to 1.49 ± 0.23 μV. The RSNA-AP relationship was shifted toward higher AP values, and its maximum gain was significantly ( P < 0.01) increased from 9.0 ± 1.3 to 16.2 ± 2.1 normalized units (NU)/mmHg. The latter effect was secondary to an increase ( P < 0.01) in the range of the RSNA variation from 285 ± 33 to 619 ± 59 NU...
American Journal of Physiology-Heart and Circulatory Physiology, 2013
Recent data indicate the brain angiotensin-converting enzyme/ANG II/AT1 receptor axis enhances emotional stress responses. In this study, we investigated whether its counterregulatory axis, the angiotensin-converting enzyme 2 (ACE2)/ANG-(1–7)/Mas axis, attenuate the cardiovascular responses to acute emotional stress. In conscious male Wistar rats, the tachycardia induced by acute stress (air jet 10 l/min) was attenuated by intravenous injection of ANG-(1–7) [Δ heart rate (HR): saline 136 ± 22 vs. ANG-(1–7) 61 ± 25 beats/min; P < 0.05]. Peripheral injection of the ACE2 activator compound, XNT, abolished the tachycardia induced by acute stress. We found a similar effect after intracerebroventricular injections of either ANG-(1–7) or XNT. Under urethane anesthesia, the tachycardia evoked by the beta-adrenergic agonist was markedly reduced by ANG-(1–7) [ΔHR: saline 100 ± 16 vs. ANG-(1–7) 18 ± 15 beats/min; P < 0.05]. The increase in renal sympathetic nerve activity (RSNA) evoked b...
Autonomic Neuroscience, 2002
In conscious, chronically instrumented rabbits (n = 7), airjet stress evoked increases in arterial pressure (AP) and renal sympathetic nerve activity (RSNA), which were greatest in the first 2 min ( + 10 mm Hg and + 127%, respectively), but then rapidly reached a stable level ( + 7 mm Hg and + 37%, respectively). Bilateral microinjection into the rostral ventrolateral medulla (RVLM) of an ionotropic excitatory amino acid (EAA) receptor antagonist kynurenate (10 nmol/200 nl) did not affect resting AP and RSNA, but reduced their initial peak responses to airjet by 80% and 52%, respectively, without altering the stable levels of these responses. By contrast, bilateral microinfusion of glutamate (2 nmol/20 nl/min) into the RVLM increased resting AP by 13 mm Hg, but did not alter the RSNA and AP responses to airjet stress. These results suggest that the RVLM is an essential site for conveying excitatory environmental influences to the sympathetic nervous system in conscious rabbits. The EAA receptors are critically important in initiating the pressor and sympathoexcitatory responses to acute emotional stress, but play relatively little role in the maintenance of these responses. D
Neuroscience, 2014
We tested the hypothesis that the angiotensinergic neurotransmission, specifically in the paraventricular nucleus of the hypothalamus (PVN), is involved in the cardiovascular modulation during acute restraint stress (RS) in rats. The intravenous pretreatment with the angiotensin AT1 receptor antagonist losartan (5 mg/kg) inhibited the pressor response to RS, but did not affect the concomitant RS-evoked tachycardiac response. Because similar effects were observed after the PVN pretreatment with CoCl 2 , and considering the high density of angiotensin receptors reported in the PVN, we studied the effect of the pretreatment of the PVN with either losartan or the angiotensin-converting enzyme (ACE) inhibitor lisinopril on the RS-evoked cardiovascular response. The bilateral microinjection of losartan (0.5 nmol/100 nL) or lisinopril (0.5 nmol/100 nL) into the PVN inhibited the RS-related pressor response without affecting the tachycardiac response, suggesting that the PVN angiotensinergic neurotransmission modulates the vascular component of the stress response. Finally, to exclude the possibility that centrally injected drugs could be leaking to the circulation and acting on peripheral vascular receptors, we tested the effect of the intravenous pretreatment with either losartan (0.5 nmol/animal) or lisinopril (0.5 nmol/animal), assuming the hypothesis of a total spread of drugs from the CNS to the peripheral circulation. When animals were pretreated with such doses of either losartan or lisinopril, the cardiovascular RS-evoked response was not affected, thus indicating that even if there were a complete leakage of the drug to the periphery, it would not affect the cardiovascular response to RS. This observation favors the idea that the effect of the intravenous injection of 5 mg/kg of losartan on the RS-related cardiovascular response would be explained by an action across the blood-brain barrier, possibly in the PVN. In conclusion, the results suggest that an angiotensinergic neurotransmission in the PVN acting on AT1-receptors modulates the vascular component of the RS-evoked cardio-vascular response.
Biomedizinische Technik/Biomedical Engineering, 2006
This study investigates the contribution of central vasopressin receptors in the modulation of systolic arterial pressure (SAP) and heart rate (HR) response to air-jet stress in conscious Wistar rats equipped with a femoral arterial catheter and intracerebroventricular cannula using novel non-peptide and selective vasopressin V 1a (SR49059) and V 1b (SSR149415) antagonists. The effects of stress on SAP and HR were evaluated by measuring the maximal response to stress, the latency of the maximal response, the duration of the recovery period, and the increase in the low frequency (LF) short-term variability component. Stress induced a parallel and almost immediate increase in both SAP and HR, followed by enhanced LF SAP variability in the recovery period. Pretreatment of rats with V 1a antagonist did not affect the maximal increase or the latency of SAP and HR response to acute stress, but shortened the recovery period of SAP and HR and prevented the increase in LF SAP. The V 1b antagonist reduced the maximal increase in SAP without affecting HR and their latencies, shortened the recovery period of SAP and inhibited the increase in LF SAP variability. These results indicate that both central V 1a and V 1b receptors mediate cardiovascular changes induced by air-jet stress in conscious rats.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012
The rise in blood pressure during an acute aversive stress has been suggested to involve activation of angiotensin type 1A receptors (AT 1A Rs) at various sites within the brain, including the rostral ventrolateral medulla. In this study we examine the involvement of AT 1A Rs associated with a subclass of sympathetic premotor neurons of the rostral ventrolateral medulla, the C1 neurons. The distribution of putative AT 1A R-expressing cells was mapped throughout the brains of three transgenic mice with a bacterial artificial chromosomeexpressing green fluorescent protein under the control of the AT 1A R promoter. The overall distribution correlated with that of the AT 1A Rs mapped by other methods and demonstrated that the majority of C1 neurons express the AT 1A R. Cre-recombinase expression in C1 neurons of AT 1A R-floxed mice enabled demonstration that the pressor response to microinjection of angiotensin II into the rostral ventrolateral medulla is dependent upon expression of the AT 1A R in these neurons. Lentiviral-induced expression of wild-type AT 1A Rs in C1 neurons of global AT 1A R knock-out mice, implanted with radiotelemeter devices for recording blood pressure, modulated the pressor response to aversive stress. During prolonged cage-switch stress, expression of AT 1A Rs in C1 neurons induced a greater sustained pressor response when compared to the control viral-injected group (22 Ϯ 4 mmHg for AT 1A R vs 10 Ϯ 1 mmHg for GFP; p Ͻ 0.001), which was restored toward that of the wild-type group (28 Ϯ 2 mmHg). This study demonstrates that AT 1A R expression by C1 neurons is essential for the pressor response to angiotensin II and that this pathway plays an important role in the pressor response to aversive stress.
The Role of AT(1A) Receptors in Cardiovascular Reactivity to Acute Aversive Stress
Hypertension
We determined whether genetic deficiency of angiotensin II Type 1A (AT 1A ) receptors in mice results in altered neuronal responsiveness and reduced cardiovascular reactivity to stress. Telemetry devices were used to measure mean arterial pressure, heart rate, and activity. Before stress, lower resting mean arterial pressure was recorded in AT 1A