Reduced Cardiovascular Reactivity to Stress but Not Feeding in Renin Enhancer Knockout Mice (original) (raw)
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American journal of hypertension, 2010
Schlager inbred hypertensive mice (BPH/2J) have been suggested to have high blood pressure (BP) due to an overactive sympathetic nervous system (SNS). The brain nuclei associated with the hypertension are also those involved in the integration of the cardiovascular responses to stress. Therefore, in the present study, we hypothesize that an increased contribution of the SNS in BPH/2J mice may culminate in a greater pressor response to stressful stimuli in these hypertensive mice than normotensive (BPN/3J) mice. Male hypertensive BPH/2J and normotensive BPN/3J mice were implanted with telemetry devices and exposed to a series of behavioral "stress" tests including aversive stress (shaker, clean cage switch, and restraint) and nonaversive stress (feeding). Aversive stress caused a 67-88% greater pressor response in BPH/2J compared with BPN/3J mice. By contrast, the feeding-induced pressor response was not different between groups. All stressors induced tachycardia that was l...
Clinical and Experimental Pharmacology and Physiology, 2006
1. Blood pressure (BP) and heart rate (HR) increase 6 and 24 h after sinoaortic baroreceptor denervation (SAD), whereas plasma renin activity (PRA) and renal renin mRNA levels remain unchanged. We postulated that a simultaneous rise in BP could offset the expected activation of renin associated with an increased renal sympathetic discharge secondary to SAD. 2. To test this hypothesis, the increase in BP associated with the onset of SAD was prevented by a continuous infusion of sodium nitroprusside (SNP; 30 microg/kg per h). Changes were measured in five groups of conscious adult male Wistar rats: (i) sham; (ii) SAD; (iii) SAD rats in which the BP was prevented from increasing by infusion of SNP; (iv) sham rats in which the BP was increased by 30% by infusion of phenylephrine (PE; 1.5-2.0 mL/h); and (v) SNP + PE for 3 h by infusion as above. 3. As expected, BP and heart rate (HR) increased significantly following SAD compared with sham rats (152 +/- 4 vs 116 +/- 3 mmHg, respectively, for BP and 503 +/- 6 vs 345 +/- 13 b.p.m., respectively for HR; n = 5; P < 0.05) but remained unchanged when SNP was infused for 3 h (106 +/- 1 mmHg and 455 +/- 9 b.p.m., respectively; n = 5; P < 0.05). 4. Similarly, BP and HR increased with PE infusion compared with PE + SNP (138 +/- 9.9 vs 113 +/- 2.3 mmHg for BP, respectively, and 325 +/- 9 vs 423 +/- 18 b.p.m. for HR, respectively; n = 5; P < 0.05). 5. Plasma renin activity remained unchanged in SAD compared with sham rats (1.67 +/- 0.35 vs 1.05 +/- 0.17 ng angiotensin (Ang) I/mL per h), but increased significantly when hypertension was prevented (5.86 +/- 0.77 ng AngI/mL per h; n = 5; P < 0.05). Renin mRNA levels in the kidneys were unchanged in all groups. 6. These results show that an elevation in BP appears to offset increased renal sympathetic discharge with no change in PRA.
AJP: Regulatory, Integrative and Comparative Physiology, 2006
The dorsomedial hypothalamus (DMH) is critically implicated in the cardiovascular response to emotional stress. This study aimed to determine whether the DMH is also important in cardiovascular arousal associated with appetitive feeding behavior and, if so, whether locally released angiotensin II and glutamate are important in this arousal. Emotional (air-jet) stress and feeding elicited similar tachycardic (+51 beats/min and +45 beats/min, respectively) and pressor (+16 mmHg and +9 mmHg) responses in conscious rabbits. Bilateral microinjection of GABA A agonist muscimol (500 pmol) into the DMH, but not nearby hypothalamic regions, attenuated pressor and tachycardic responses to air-jet by 56-63% and evoked anorexia.
Increased (Pro)renin Receptor Expression in the Hypertensive Human Brain
Frontiers in Physiology, 2020
Overactivation of the renin-angiotensin system (RAS)-a central physiological pathway involved in controlling blood pressure (BP)-leads to hypertension. It is now well-recognized that the central nervous system (CNS) has its own local RAS, and the majority of its components are known to be expressed in the brain. In physiological and pathological states, the (pro)renin receptor (PRR), a novel component of the brain RAS, plays a key role in the formation of angiotensin II (Ang II) and also mediates Ang II-independent PRR signaling. A recent study reported that neuronal PRR activation is a novel mechanism for cardiovascular and metabolic regulation in obesity and diabetes. Expression of the PRR is increased in cardiovascular regulatory nuclei in hypertensive (HTN) animal models and plays an important role in BP regulation in the CNS. To determine the clinical significance of the brain PRR in human hypertension, we investigated whether the PRR is expressed and regulated in the paraventricular nucleus of the hypothalamus (PVN) and rostral ventrolateral medulla (RVLM)-two key cardiovascular regulatory nuclei-in postmortem brain samples of normotensive (NTN) and HTN humans. Here, we report that the PRR is expressed in neurons, but not astrocytes, of the human PVN and RVLM. Notably, PRR immunoreactivity was significantly increased in both the PVN and RVLM of HTN subjects. In addition, PVN-PRR immunoreactivity was positively correlated with systolic BP (sBP) and showed a tendency toward correlation with age but not body mass index (BMI). Collectively, our data provide clinical evidence that the PRR in the PVN and RVLM may be a key molecular player in the neural regulation of BP and cardiovascular and metabolic function in humans. Keywords: (pro)renin receptor/(P)RR, human hypertension, paraventricular nucleus of the hypothalamus, rostral ventrolateral medulla, renin-angiotensin system
Brain renin-angiotensin system in hypertension, cardiac hypertrophy, and heart failure
Frontiers in Physiology, 2012
Brain renin-angiotensin system (RAS) is significantly involved in the roles of the endocrine RAS in cardiovascular regulation. Our studies indicate that the brain RAS participates in the development of cardiac hypertrophy and fibrosis through sympathetic activation. Inhibition of sympathetic hyperactivity after myocardial infarction through suppression of the brain RAS appears beneficial. Furthermore, the brain RAS modulates the cardiovascular and fluid-electrolyte homeostasis not only by interacting with the autonomic nervous system but also by modulating hypothalamic-pituitary axis and vasopressin release. The brain RAS is also involved in the modulation of circadian rhythms of arterial pressure, contributing to non-dipping hypertension. We conclude that the brain RAS in pathophysiological states interacts synergistically with the chronically overactive RAS through a positive biofeedback in order to maintain a state of alert in diseased conditions, such as cardiac hypertrophy and failure. Therefore, targeting brain RAS with drugs such as renin or angiotensin converting enzyme inhibitors or receptor blockers having increased brain penetrability could be of advantage.