Vasoconstrictor action of angiotensin I-convertase and the synthetic substrate (Pro11,D-Ala12)-angiotensin I.

Abstract

A chymase (also referred to as angiotensin I-convertase) specific for the conversion of angiotensin (Ang) I to Ang II has been identified in human heart. This serine protease is also present in dog and marmoset vasculature. We examined the vasoconstrictor effects of Ang II putatively generated from an angiotensin-converting enzyme (ACE)-resistant convertase synthetic substrate (SUB) in vivo and in vitro. In marmosets, SUB (7 to 700 /ig/kg IV) or Ang I (0.1 to 30 /ig/kg) caused similar dose-dependent increases in mean arterial pressure (10 to 100 mm Hg) and decreases in heart rate. Pressor effects of SUB were slightly attenuated at low (but not high) doses by captopril (CAP, 1 mg/kg IV) and blocked by losartan (5 mg/kg IV); in contrast Ang I pressor effects were substantially blocked by both. In isolated canine superior mesenteric artery, Ang I-induced contraction was

Functional role, cellular source, and tissue distribution of rat elastase-2, an angiotensin II-forming enzyme

“…Similarly, chymostatin inhibits both chymases (56,59) and elastase-2 (47), so the use of Ac-AAPL-CK and chymostatin cannot unequivocally indicate the relative contribution of different serine proteases in the generation of ANG II in the isolated rat MAB or elsewhere. However, as established in literature, rat chymase is mainly an angiotensinase (6,30,62), which argues in favor of elastase-2 being responsible for the ACE-independent pathway for ANG II generation in the rat MAB because it does not degrade ANG II (47,52 ]-ANG I are either homologous to human heart chymase (22,38,41,43,63) or rat elastase-2 (52), so this latter enzyme is the only known rat protease fitting the experimental evidence described for the ACE-independent pathway for ANG II generation in the rat MAB. ]-ANG I in the isolated MAB was abolished by the ANG II receptor antagonist saralasin (50 nM) in the perfusion solution (Fig.…”

“…In other investigations, the partial or total blockade of ANG II formation by different combinations of ACE inhibitors with chymostatin or other protease inhibitors has provided clues as to the nature of the enzymes involved in ANG I conversion in a particular tissue or pharmacological preparation (23,45). Since the advent of [Pro 11 ,D-Ala 12 ]-ANG I, a biologically inactive precursor that selectively yields ANG II on incubation with chymases but not with ACE or carboxypeptidases (22), several reports (18,22,26,38,41,43,61,63) have described the relative contribution of chymases in ANG II formation in isolated preparations derived from various species.The vascular endothelium actively participates in the control of vascular tone through the synthesis and metabolism of several vasoactive substances (1). In particular, the vascular endothelium has been shown to be a major site of conversion of circulating ANG I to ANG II by ACE located on its luminal surface (2).…”

Pivotal Role of Mouse Mast Cell Protease 4 in the Conversion and Pressor Properties of Big-Endothelin-1

“…In the human cardiovascular system, mast cell-derived serine protease chymase generates the vasoconstrictor peptide angiotensin II (Ang-II), especially in the heart and the vascular wall (Urata et al, 1993;Mangiapane et al, 1994). Chymase, similarly to the angiotensin converting enzyme, cleaves the precursor angiotensin-I to yield the biologically active Ang-II (Urata et al, 1990).…”

Phytochemical and in vitro and in vivo biological investigation on the antihypertensive activity of mango leaves (Mangifera indica L.)

“…administration of an association between ketamine (80 mg/kg) and xylazine (15 mg/kg) and catheterized (femoral artery and vein) according to Andrade and colleagues [Andrade et al 2012]. The ACE inhibitory activity assay was performed as described by Mangiapane and colleagues [Mangiapane et al 1994, with minor modifications. The following groups were used: captopril (C; n = 5) received an intravenous (IV) dose of 30 mg/kg; and the dichloromethanic fraction (n = 5) received an IV dose of 100 mg/kg.…”