ANGIOTENSIN II‐MEDIATED VASODILATION IS REDUCED IN ADULT SPONTANEOUSLY HYPERTENSIVE RATS DESPITE ENHANCED EXPRESSION OF AT₂ RECEPTORS

Abstract

1. The vasodilator action of angiotensin (Ang) II has not yet been demonstrated in spontaneously hypertensive rats (SHR), nor have any possible changes in this response during the development of hypertension. 2. In the present study, the vasodilator effect of AngII was evaluated in the rat isolated, preconstricted mesenteric arterial bed (MAB) from 6- (young) and 24-week-old (adult) SHR and compared with effects on MAB from age-matched normotensive rats (control). 3. Angiotensin II (10-300 nmol) induced vasodilation in noradrenaline (NA)-preconstricted MAB that was greater in vessels from young compared with adult rats in both the control and SHR groups. Angiotensin II-induced vasodilation was reduced by the angiotensin AT(2) receptor antagonist PD 123319 (10 micromol/L), the angiotensin-(1-7) receptor antagonist A779 (1 micromol/L) and the bradykinin B(2) receptor antagonist HOE-140 (0.01 micromol/L), but not by the AT(1) receptor antagonist losartan (30 micromol/L). Expression of AT(2) receptors was weak in vessels from adult control rats compared with that in young control rats, whereas in young SHR AT(2) receptor expression was increased compared with that in young control rats. This increased expression of AT(2) receptors was maintained in adult SHR and there was no significant difference in AT(2) receptor expression between young and old SHR. 4. The findings of the present suggest that AngII induces an AT(2) receptor-mediated vasodilator effect in the MAB via activation of angiotensin-(1-7) and bradykinin receptors, an action that is reduced in adult control rats and adult SHR. In adult control rats, the attenuated response of AngII is probably due to endothelial dysfunction and reduced expression of AT(2) receptors, whereas in adult SHR it is associated with endothelial dysfunction alone. Increased expression of AT(2) receptors in SHR may represent a counteracting response for modulating blood pressure.

Role of renin–angiotensin system and oxidative status on the maternal cardiovascular regulation in spontaneously hypertensive rats

“…These novel data in female rats confirm previous findings on rabbit microperfused afferent arteriole 30 and rat perfused mesenteric arteries from male normotensive rats 7,31 showing that the vasodilator response of Ang II is endothelium-dependent and mediated by activation of NO-cGMP pathway. 7 This vasodilator effect of Ang II was also demonstrated by our group in MAB from male SHR, 8 showing that increased AT 2 receptor expression, maintained with age, represents an additional benefit of the hemodynamic effects of AT 1 receptor antagonists used as antihypertensive therapy.…”

“…In contrast, the AT 2 receptor appears to counteract some or all of the aforementioned effects mediated via AT 1 receptors on vascular response, BP, and cellular growth. [6][7][8] Angiotensin 1-7 (Ang-(1-7)) is formed from Ang II by angiotensin-converting enzyme 2 (ACE2) and has been shown to provide a modulator effect of the RAS via mas receptor. 9 This peptide promotes effects opposed to those mediated by Ang II via AT 1 receptor, including vasodilation.…”

Angiotensin II Type 2 Receptor–Mediated and Nitric Oxide–Dependent Renal Vasodilator Response to Compound 21 Unmasked by Angiotensin-Converting Enzyme Inhibition in Spontaneously Hypertensive Rats In Vivo

“…This is in line with our observation of a higher abundance of AT 2 R in SHR compared with WKY rats, as also reported earlier by others and with previous studies showing unmasking of AT 2 R-mediated effects of AngII by AT 1 R blockade. 5,6,16,19 Fenoldopam, administered at the end of each experiment, significantly increased RBF in all animals, indicating that the lack of vasodilator response to C21 in WKY rats cannot be attributed to decreased sensitivity of the experimental setup to detect renal vasodilation.…”

“…1 Renal AT 2 Rs are also upregulated in response to sodium depletion 2 or kidney damage 3 in obese Zucker rats 4 and spontaneously hypertensive rats (SHR). 5,6 Current evidence suggests that the AT 2 R plays a counterregulatory role opposing the AT 1 R-mediated actions by promoting depressor effects, vasodilation, and natriuresis. 7 AngII has been shown to induce vasodilation through AT 2 R stimulation in conditions associated with AT 1 R blockade and AT 2 R upregulation.…”

Casein-derived tripeptide Ile–Pro–Pro improves angiotensin-(1–7)- and bradykinin-induced rat mesenteric artery relaxation

“…to the involvement of bradykinin (Carey et al 2001;Soares de Moura et al 2004). However, there are only few studies concerning the vasodilator action of Ang II in SHR (Ognibene et al 2009). In the present study, Ang II produced relaxations in phenylephrine-precontracted mesenteric arteries, which were neither dependent on AT 1 -nor AT 2 -receptor, as the blockade of these receptors first by valsartan and then by valsartan and PD123319 did not affect the relaxation.…”