The role of bradykinin, AT₂ and angiotensin 1–7 receptors in the EDRF‐dependent vasodilator effect of angiotensin II on the isolated mesenteric vascular bed of the rat

Abstract

1 The mechanisms involved in the vasodilator actions of angiotensin II (Ang II) have not yet been completely elucidated. We investigated the potential mechanisms that seem to be involved in the Ang II vasodilator effect using rat isolated mesenteric vascular bed (MVB). 2 Under basal conditions, Ang II does not affect the perfusion pressure of MVB. However, in vessels precontracted with norepinephrine, Ang II induces vasodilation followed by vasoconstriction. Vasoconstrictor, but not the vasodilation of Ang II, is inhibited by AT 1 antagonist (losartan). The vasodilator effect of Ang II was not inhibited by AT 2 , angiotensin IV and angiotensin 1-7 receptor antagonists alone (PD 123319, divalinal, A 779, respectively). 3 The vasodilator effect of Ang II is significantly reduced by endothelial removal (deoxycholic acid), but not by indomethacin. Inhibition of NO-synthase by N G -nitro-L-arginine methyl ester (L-NAME) and guanylyl cyclase by 1H-[1,2,3] oxadiazolo [4,4-a] quinoxalin-1-one (ODQ) reduces the vasodilator effect of Ang II. This effect is also reduced by tetraethylammonium (TEA) or L-NAME, and a combination of L-NAME plus TEA increases the inhibitory effect of the antagonists alone. However, indomethacin does not change the residual vasodilator effect observed in vessels pretreated with L-NAME plus TEA. 4 In vessels precontracted with norepinephrine and depolarized with KCl 25 mM or treated with Ca 2 þ -dependent K þ channel blockers (charybdotoxin plus apamin), the effect of Ang II was significantly reduced. However, this effect is not affected by ATP and voltage-dependent K þ channel blockers (glybenclamide and 4-aminopyridine). 5 Inhibition of kininase II with captopril significantly potentiates the vasodilator effect of bradykinin (BK) and Ang II in the rat MVB. The inhibitory effect of the B 2 receptor antagonist HOE 140 on the vasodilator effect of Ang II is further enhanced by PD 123319 and/or A 779.

Analysis of the Vasorelaxant Action of Angiotensin II in the Isolated Rat Renal Artery

“…The role of K + channels in angiotensin II-mediated vasorelaxation has been already described (10,21). Our results have shown that apamin, a selective blocker of the low-conductance Ca…”

“…Thus, we may suggest that SK Ca , K ir , and K ATP channels most probably do not participate in RRA response to angiotensin II. In accordance to this finding, Dimitroupoulou et al (11) and De Moura et al (21) found that activation of SK Ca , K ir , and K ATP are not involved in the angiotensin IIinduced rat mesenteric artery relaxation. On the other hand, we have shown that administration of TEA or charybdotoxin (a blocker of large-conductance Ca 2+ -activated K + channels) produced significant but not complete inhibition of angiotensin II-induced relaxation.…”

Enhanced angiotensin II production by renal mesangium is responsible for apoptosis/proliferation of endothelial and epithelial cells in a model of malignant hypertension

“…Angiotensin II has been shown previously to stimulate exaggerated apoptosis in a variety of cells [32][33][34][35], including endothelial cells, which possess receptors to angiotensin II on their membranes [36,37]. For the HUVEC cell line, the protocols for angiotensin IIinduced apoptosis are usually based on at least 18 h incubation [38,39], which was not the case in our experimental set-up.…”

Advances in the Renin Angiotensin System

“…Weak vasodilator actions of Ang-(1–7) given systemically contrasts with the more pronounced effects of the peptide when administered to isolated blood vessels (Almeida et al, 2000; Brosnihan et al, 1996, 1998; Fernandes et al, 2001; Gorelik et al, 1998; Kozlovski et al, 2007; Machado et al, 2002; Meng & Busija, 1993; Neves et al, 2004; Oliveira et al, 1999; Osei et al, 1993; Sampaio et al, 2007; Soares de et al, 2004; Tirapelli et al, 2006), a finding that underscores a paracrine rather than a systemic effect of this angiotensin peptide. There is agreement that Ang(1–7) vasodilator responses are in part related to release of bradykinin and endothelium-derived nitric oxide as well as a direct effect of Ang-(1–7) on the mas-R (Almeida et al, 2000; Brosnihan et al, 1996, 1998; Davie & McMurray, 1999; Fernandes et al, 2001; Gorelik et al, 1998; Heitsch et al, 2001; Kozlovski et al, 2007; Lemos et al, 2005; Li et al, 1997a; Li et al, 1997b: Marangoni et al, 2006; Oliveira et al, 1999, 2002, 2003; Sampaio et al, 2007; Soares de et al, 2004; Tirapelli et al, 2006).…”