Characterization of the angiotensin II-receptor subtype in the longitudinal smooth muscle of the rat portal vein

Abstract

The purpose of the present study was to identify the angiotensin II-receptor subtype involved in the enhancement of the amplitude of the phasic contractions by angiotensin II in the isolated rat portal vein preparation. At an extracellular Ca2+ concentration of 0.9 mmol/l and a K+ concentration of 4 mmol/l, angiotensin II induced concentration-dependent increases in the amplitude of the phasic contractions. The enhancement of phasic contraction amplitude caused by angiotensin II was not significantly altered by pretreatment of the rat portal vein with indomethacin 10(-5) mol/l or nitro-L-arginine 10(-4) mol/l, indicating that neither prostaglandins nor the endothelium derived-relaxing factor (NO) are involved. Losartan (DuP 753), a nonpeptide selective AT1-receptor antagonist, concentration-dependently shifted the concentration-response curve for the effect of angiotensin II on the amplitude of the contractions to the right, without reducing the maximal response (pA2 = 8.6, slope = 0.98), thus suggesting competitive antagonism at the level of AT1-receptors. By contrast, PD 123,177, a nonpeptide selective AT2-receptor antagonist, even at 10(-5) mol/l, caused no significant change of the phasic myogenic response to angiotensin II, indicating the absence of AT2-receptor involvement. Dithiothreitol, a disulfide-reducing agent which is known to inactivate AT1-receptors in various tissues, markedly inhibited (3 mmol/l) or even abolished (5 mmol/l) the contractile response of the rat portal vein to angiotensin II, supporting the conclusion that these receptors can be classified as AT1-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

A Systematic Comparison of the Properties of Clinically Used Angiotensin II Type 1 Receptor Antagonists

“…Most of this work has been carried out in isolated blood vessels. The vast majority of in vitro studies on ARB effects on ANG-induced vasoconstriction has been performed with isolated rabbit aorta, but some findings have also been reported, e.g., for rat aorta , rat portal vein (Zhang et al, 1993;Morsing et al, 1999), guinea pig aorta (Mizuno et al, 1995;Hashimoto et al, 1997), rabbit mesenteric artery , dog pulmonary artery (Guimarães et al, 2011), pig and human coronary artery (Maassen vandenBrink et al, 1999), or human gastroepiploic artery (Jin et al, 1997) or human subcutaneous microvessels (Garcha et al, 1999); data with compounds that have been tested in multiple preparations indicate that the antagonist potency of a given ARB is comparable across species and vascular beds. On the basis of these studies the various ARBs appear to have the following affinity estimates (pA 2 for surmountable or pD 2 for insurmountable ARBs; median with 95% confidence intervals) at mammalian vascular AT1R ( Fig.…”

“…Such inhibition has been reported for azilsartan (Kohara et al, 1996), candesartan Wada et al, 1994Wada et al, , 1996Kohara et al, 1996;Nakano et al, 1997;Champion et al, 1998;Koike et al, 2001;Maillard et al, 2002a), eprosartan (Wang and Brooks, 1992), irbesartan Lacour et al, 1994;Christophe et al, 1995;Culman et al, 1999;Maillard et al, 2002a), losartan (Wong et al, 1990a,c; Abdelrahman (Wong et al, 1990b,d;Buhlmayer et al, 1991;Edwards et al, 1992a;Lin et al, 1992;Liu et al, 1992b;Bernhart et al, 1993;Cazaubon et al, 1993;Criscione et al, 1993;Leung et al, 1993;Noda et al, 1993;Shibouta et al, 1993;Dickinson et al, 1994;Schambye et al, 1994;Keiser et al, 1995;Mizuno et al, 1995;Hashimoto et al, 1997;Jin et al, 1997;Tamura et al, 1997a;Garcha et al, 1999;Inada et al, 1999;Maassen vandenBrink et al, 1999;Morsing et al, 1999;Balt et al, 2002;Guimarães et al, 2011;Wienen et al, 1992Wienen et al, , 1993Zhang et al, 1993…”

Physiological and Pathophysiological Functions of the AT 2 Subtype Receptor of Angiotensin II

“…Briefly, AT 2 Rs are present in the uterus, 9,10 the kidney, 11,12 rat (Wistar-Kyoto rats and spontaneously hypertensive rats [SHR]) mesentery, [13][14][15] the portal circulation, 16 the heart, 17 and the brain. 18 Whereas the aorta has been the most commonly used model in the investigation of AT 2 R functions (see below), in small resistance arteries AT 2 Rs are also present in the endothelial and/or smooth muscle cells, depending on the vessel type and species.…”

Are Multiple Angiotensin Receptor Types Involved in Angiotensin (1-7) Actions on Isolated Rat Portal Vein?

“…This effect of Ang II has been demonstrated to be mediated predominantly by AT 1 -receptors, which represent about 75% of the Ang II specific binding sites at this level. [1][2][3][4][5] Angiotensin (1)(2)(3)(4)(5)(6)(7) [Ang (1-7)] is a vasoactive angiotensin peptide that retains some of the actions ascribed to Ang II and counteracts others. There are many studies describing the effects of Ang (1-7) on cultured vascular smooth muscle cells (VSMCs), arterial rings and intact vessels.…”

“…These Ang (1-7) effects are dose-dependent and are sometimes opposite to the effects of Ang II. In the micromolar range, Ang (1-7) effects are mediated by AT 1 , AT 2 or Ang (1-7) -specific receptors. [6][7][8][9][10][11][12][13] Some authors have demonstrated that relaxant effects of Ang (1-7) at these concentrations are dependent on the presence of the intact endothelium.…”