Effects of complete renal denervation and selective afferent renal denervation on the hypertension induced by intrarenal norepinephrine infusion in conscious rats.

To test the hypothesis that continuous intrarenal norepinephrine (NE) infusions produce hypertension via activation of afferent renal nerves (ARN), rats were subjected to complete renal denervation (RN-x), selective renal deafferentation (ARN-x) or sham surgery, prior to infusion of NE. In the pre-infusion period, mean arterial pressure (MAP) was significantly lower in RN-x than in ARN-x or sham-operated rats. Plasma renin concentration (PRC) was significantly reduced following ARN-x, but not RN-x. During 5-day intrarenal infusions of 4, 12 or 36 micrograms NE/kg per h, MAP rose to similar levels in RN-x and sham-RN-x rats. However, RN-x rats exhibited significantly elevated PRC levels, suggesting that denervation supersensitivity masked the possible effects of RN-x. In sham-RN-x rats, MAP increased significantly more during intrarenal infusion of 12 micrograms NE/kg per h than during intravenous infusion of the same amount. In ARN-x rats, MAP rose to a similar degree during intravenous and intrarenal infusions. The pressor responses in the ARN-x rats, however, were not significantly smaller at any point than those in intact rats. PRC rose to comparable levels in ARN-x and intact rats. Thus, in normotensive rats, efferent renal nerves (ERN) but not ARN are of functional significance in maintaining basal blood pressure. ARN may be involved in the control of renin release. Since neither RN-x nor ARN-x attenuated the development of hypertension, renal nerves are not necessary for the full expression of hypertension in this model.

Role of afferent renal nerves in spontaneous hypertension in rats.

In the present study we examined sympathetic function and baroreceptor reflex sensitivity in adult spontaneously hypertensive rats (SHR) after a selective transection of afferent renal nerves in the prehypertensive and established phases of hypertension. Renal deafferentation performed between 3 and 4 weeks after birth did not influence the course of the development of high blood pressure when compared with sham-operated rats. Mean arterial pressure, heart rate, and plasma norepinephrine concentrations were similar in both groups when measured at 13 weeks after renal deafferentation. However, blood pressure responses to ganglionic blockade with hexamethonium were significantly reduced in the renal deafferented SHR. Baroreceptor reflex sensitivity, assessed by heart rate responses to blood pressure changes induced by phenylephrine and nitroprusside, was significantly enhanced in these rats. When renal deafferentation was performed in adult SHR with established hypertension, mean arterial pressure decreased slightly but significantly by 5%. Heart rate, plasma norepinephrine concentrations, and responses to hexamethonium were not affected by this procedure. However, in the renal deafferented adult SHR, heart rate responses to phenylephrine but not to nitroprusside were significantly increased. Thus, in contrast to efferent renal nerves, afferent renal nerves do not play an important role in the development and maintenance of high blood pressure in SHR, but may contribute to the mechanisms that alter sympathetic function and baroreceptor reflex sensitivity in SHR during the development of hypertension.

Beta-adrenoceptors in kidney tubules of spontaneously hypertensive and normotensive rats.

Beta-adrenoceptor binding characteristics were determined in different fractions of rat kidney tubules using a [125Iodo]-(-)-cyanopindolol (ICYP) binding assay. The highest amount of binding sites was found in a fraction containing predominantly distal tubular fragments. In a separate series of experiments the ICYP binding characteristics were compared in whole tubular fractions from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) of different ages. The maximum number of binding sites was significantly higher both in young (3 weeks) and adult (14 weeks) SHR when compared to age-matched WKY. These studies showed the presence of beta-adrenoceptor binding sites in rat kidney tubules and support the potential importance of tubular beta-adrenoceptors in the development of spontaneous hypertension and in the mechanism of antihypertensive action of beta-blockers.