Neural contribution to renal hypertension following acute renal artery stenosis in conscious rats.

Abstract

SUMMARY To assess the hemodynamic changes during acute renal artery stenosis (RSt) and their dependence on alterations in the renin-angiotensin and sympathetic nervous systems, we studied conscious rats chronically instrumented with miniaturized pulsed-Doppler flow probes. Probes were implanted on the superior mesenteric and both renal arteries, and on the lower abdominal aorta for measurement of mesenteric (MR), renal (RR), and hindquarters (HQR) vascular resistance. Unilateral RSt, with a pneumatic cuff occluder that reduced flow by approximately 50%, increased mean arterial pressure (MAP) by 32%, reduced heart rate, and increased MR, nonstenotic (contralateral) RR and HQR. The hypertension was renin-dependent since plasma renin activity increased 6-fold and the angiotensin II (All) antagonist, saralasin, significantly reduced MAP and regional resistances. The acute hypertension was also associated with increased neurogenic vasoconstrictor tone since hexamethonium markedly reduced MAP, MR, HQR and non-stenotic RR. Hexamethonium similarly decreased MAP during hypertension induced by AH infusion, whereas hypertension produced by the "pure" peripheral vasoconstrictor, phenylephrine, was unaffected by ganglionic blockade. In animals with peripheral sympathectomy produced by 6-hydroxydopamine, acute RSt produced hemodynamic changes similar in magnitude to intact animals; however, PRA increased 3-fold more than in intact rats. We conclude that hypertension induced by acute RSt in conscious rats is not only renindependent, but is also associated with inappropriately high neurogenic vasoconstrictor tone, presumably activated by indirect neural actions of AH. has received intensive study, knowledge concerning both the mechanisms that maintain hypertension and produce the initial disturbances remains incomplete. There is, however, growing interest in the possibility that significant interactions may exist between the renin-angiotensin system (RAS) and sympathetic nervous system. It is clear from studies on plasma renin activity (PRA) and the effects of angiotensin (All) blockade that the RAS is activated at the onset of renal hypertension.'" 1 On the other hand, during the chronic phase of renal hypertension PRA is normal or only slightly elevated and All antibodies and receptor antagonists do not substantially reduce blood pressure.

Sympathetic Activation in Chronic Renal Failure

“…33 Of note, these effects are long lasting and do not occur with infusion of vehicle. 34 In conjunction with the demonstration of elevated sympathetic activity in experimental renal artery stenosis 35 Figure 1. Causes and consequences of sympathetic activation in CRF: Several forms of "renal injury" seem to have the ability to stimulate afferent signaling via sensory renal nerves.…”

Development of hypertension from unilateral renal artery stenosis in conscious dogs.

“…The autonomic nervous system could have been involved in the chronic responses to stenosis in at least two main ways: by its activity being modulated by Ang II either peripherally or centrally (See References [41][42][43] or by afferent neural input from the stenotic kidney. 6 -8 However, the results of the present study in conscious recumbent dogs did not reveal a significant role for the autonomic nervous system in the hemodynamic responses.…”

Renal nerves and the development of Dahl salt-sensitive hypertension.

“…Previous studies have suggested that sympathetic outflow may participate in the development of hypertension in rats following reduced renal perfusion pressure 24 and in dogs during intrarenal infusion of adenosine 9 or norepinephrine. 25 The present data indicate that, at least in the DS, elevation of sodium intake by an 8% sodium chloride diet does not activate renal afferent neural pathways leading to elevation of arterial pressure.…”