Role of the renin-angiotensin system in the compensation of quinpirole-induced blood pressure decrease

Abstract

The dopamine D(2)-like receptor agonist quinpirole has been reported to lower blood pressure. This effect appears to be mediated via activation of presynaptic D(2)-like receptors inhibiting the stimulated neural norepinephrine release. The aim of the present study was to investigate the role of renal nerves and the renin-angiotensin system (RAS) in the blood pressure lowering effect of quinpirole. Therefore, clearance experiments using different doses of quinpirole (0.3 to 100 microg/kg/min) were performed in thiopental-anesthetized rats with intact kidneys (INN) or 5 to 7 days after bilateral renal denervation (DNX). The functional involvement of the RAS in the blood pressure lowering effect of quinpirole was determined in rats pretreated with a subpressor dose of angiotensin II (10 microg/kg/min) or in rats pretreated with the angiotensin II (AT(1)) receptor antagonist losartan, in a subdepressor dose (10 microg/kg/min). Quinpirole dose-dependently decreased mean arterial blood pressure (MAP) by up to 29%. This blood pressure lowering effect of quinpirole was observed at lower doses in DNX rats when compared with INN animals (ED(50): 0.98 microg/kg/min in DNX vs. 6.02 microg/kg/min in INN animals). Quinpirole in a dose of 3 microg/kg/min, which did not affect MAP in vehicle treated INN rats, significantly reduced MAP in rats with losartan pretreatment. In DNX rats pretreated with angiotensin II the MAP-response to the infusion of 3 microg/kg/min quinpirole was clearly attenuated in comparison with untreated DNX animals. Our data show that stimulation of dopamine D(2)-like receptors dose-dependently decreased blood pressure, which was potentiated by both interruption of the renal innervation and AT(1) receptor blockade, while exogenous ANG II restored the enhancement of the blood pressure response to quinpirole. We conclude that the increased vasodilatory effect of quinpirole after renal denervation might depend on a decreased activity of the RAS.

The Role of Pre-junctional D2-like Receptors Mediating Quinpirole-Induced Inhibition of the Vasodepressor Sensory CGRPergic Out-flow in Pithed Rats

“…It must be highlighted that the selective agonists SKF-38393 (D 1 -like) or quinpirole (D 2 -like) did not affect the increase in diastolic blood pressure during the infusion of methoxamine in our experiments (not shown). In contrast, other studies have shown that activation of these receptors results in a dose-dependent decrease in diastolic blood pressure [20,21]. This apparent discrepancy could be due to the fact that i.v.…”

Dopamine and Renal Function and Blood Pressure Regulation

“…Blockade of AT 1 R normalizes the impaired renal vasodilator effect of D 1 -like receptor stimulation in the SHR (134). The increased vasodilatory effect of a D 3 R/D 4 R agonist (quinpirole) (203, 548) after renal denervation may also depend on a decreased activity of the renin-angiotensin system (379). …”

Effects of selective dopamine receptor subtype agonists on cardiac contractility and regional haemodynamics in rats

“…Mice lacking the D3 receptor are reported to be hypertensive and display abnormal regulation of the renin–angiotensin system 6 . However, in the rat, the effects of the D3 receptor subtype on the renin–angiotensin system and renal haemodynamics are still in question 7 . The D4 receptors are reported to be present in rat 8 and human atria 9 and have no effect on cardiac contractility 10 .…”