Short-term effects of angiotensin II blockade on renal blood flow and sympathetic activity in awake rats.

Abstract

To investigate the effects of an angiotensin II type 1 receptor antagonist (CV-11974) on renal blood flow and renal sympathetic nerve activity compared with a calcium antagonist (nicardipine), we measured both parameters in conscious spontaneously hypertensive rats aged 13 to 15 weeks. One to 2 days after surgery, CV-11974 (n = 9) and nicardipine (n = 8) were intravenously administered to decrease arterial pressure in a similar time course and degree of hypotension. CV-11974 increased renal blood flow by 23 +/- 4% at the maximal fall in mean arterial pressure (-32 +/- 1 mm Hg), and renal nerve activity increased by 70 +/- 7%. The maximal increase in renal blood flow (+27 +/- 4%) was observed when mean pressure was reduced by approximately 20 mm Hg. The maximal reduction of renal vascular resistance (-33 +/- 3%) correlated significantly with pretreatment levels of plasma renin concentration (r = -.792). In contrast, nicardipine produced a progressive reduction of renal blood flow and marked increases in heart rate and renal nerve activity. Increases in heart rate and nerve activity were greater than those with CV-11974 treatment (P < .001). At the maximal fall in mean pressure (-32 +/- 1 mm Hg), renal blood flow decreased by 23 +/- 4%, which was significantly correlated with percent changes in renal nerve activity (+150 +/- 11%, r = -.744). Renal denervation in another set of rats (n = 6) improved renal blood flow and renal vascular resistance responses to nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Nervous Kidney

“…44,45 These studies with exogenous Ang II produce limited insight into the effects of endogenous Ang II on peripheral sympathetic nerve activity. With the use of physiological interventions such as alterations in dietary sodium content 46 -48 to manipulate endogenous Ang II or animal models characterized by increased endogenous Ang II such as normal birth, 49,50 congestive heart failure, [51][52][53][54][55][56][57] and hypertension, 58,59 together with agents that interrupt the renin-angiotensin system (ACEI, Ang II AT 1 -receptor antagonist), important information on the effects of endogenous Ang II on peripheral sympathetic nerve activity has emerged.…”

“…44,45 These studies with exogenous Ang II produce limited insight into the effects of endogenous Ang II on peripheral sympathetic nerve activity. With the use of physiological interventions such as alterations in dietary sodium content 46 -48 to manipulate endogenous Ang II or animal models characterized by increased endogenous Ang II such as normal birth, 49,50 congestive heart failure, 51-57 and hypertension, 58,59 together with agents that interrupt the renin-angiotensin system (ACEI, Ang II AT 1 -receptor antagonist), important information on the effects of endogenous Ang II on peripheral sympathetic nerve activity has emerged.A general finding is that when alterations in arterial pressure are prevented either by intracerebroventricular administration of the agent or restoration of arterial pressure with infusion of appropriate vasoactive substances, agents that interrupt the renin-angiotensin system decrease the basal level of peripheral sympathetic nerve activity and shift the arterial baroreflex regulation of peripheral sympathetic nerve activity to a lower level of arterial pressure. This is exemplified in the results from intracerebroventricular administration of losartan, a nonpeptide-selective Ang II AT 1 -receptor antagonist, to rats consuming low, normal, or high dietary sodium.…”

Proximal Tubular Angiotensin II Levels and Renal Functional Responses to AT 1 Receptor Blockade in Nonclipped Kidneys of Goldblatt Hypertensive Rats

“…14 Thus, rapid acute decreases in arterial pressure caused by systemic AT 1 receptor blockade may elicit various indirect effects, including activation of the sympathetic nervous system, to increase peripheral vascular resistance and renal vascular resistance. [15][16][17] Previous studies attempting to evaluate the direct in vivo effects of intrarenal Ang II receptor blockade were compromised because the systemic infusion of receptor antagonists, even if given directly into the renal artery, leads to spillover into the systemic circulation and consequent reductions in systemic arterial pressure. 18 Recent availability of highly potent, nonsurmountable AT 1 receptor antagonists 19,20 has enabled more complete characterization of the effects of direct intrarenal Ang II blockade on the nonclipped kidneys of 2K1C Goldblatt hypertensive rats in the absence of decreases in MAP.…”

Intratubular Renin-Angiotensin System in Hypertension

“…Sodium depletion has been associated with increased number of AT1 receptors and an increased response to ARB. By binding AT1 receptors, an ARB decreases aldosterone, vasopressin, and catecholamine release ACE [89][90][91][92][93][94]. ARB also causes vascular vasodilation and inhibition of sodium and water reabsorption in the kidney.…”