Demonstration of extrapulmonary activity of angiotensin converting enzyme in intact tissue preparations

Abstract

1 The activity of angiotensin converting enzyme (ACE) has been studied on functional parameters of intact isolated preparations of extrapulmonary tissues. The conversion of angiotensin I (A I) to angiotensin II (A II) and the cleavage of bradykinin (BK) were used as indicators of ACE activity. Captopril was employed as a specific inhibitor of ACE. 2 Captopril augmented the BK-induced contractions of the rat isolated uterus, the BK-and substance P-induced contractions of the guinea-pig ileum, and the BK-induced venoconstriction in the isolated perfused ear of the rabbit. Degradation of BK by ACE was calculated to be 52% in the rat uterus and 75% in the rabbit perfused ear. 3 Captopril inhibited the A I-induced contractions of the rat isolated colon, the A I-induced vasoconstriction in the isolated perfused ear of the rabbit and the rise in blood pressure induced by i.a. injections of A I in pithed rats. Conversion of A I to A II was calculated to be 13% in the rat colon and 26% in the rabbit perfused ear. 4 From estimations of the A II activity (bioassay on the rat colon) in the effluent of the perfused ear of the rabbit after injections of A I into the arterial inflow cannula it was calculated that approximately one tenth of A I was converted to A II during a single passage through the ear (less than 15 s). 5 The present experiments suggest that the high activity of ACE in endothelium of blood vessels of extrapulmonary tissues may provide an additional (endothelium-dependent) local vasoconstrictor mechanism by the rapid formation of A II and inactivation of BK. The ACE activity in non-vascular smooth muscles, other than those of blood vessels, may also affect the physiological functions of these tissues.

Effect of oil palm phenolics on gastrointestinal transit, contractility and motility in the rat

“…From this study and previous studies with rats (Patten, Adams, Dallimore, & Abeywardena, 2004), we have determined that the potency of angiotensin I compared to angiotensin II is about 5% in agreement with the literature (Law, 1971). However, the angiotensin I in this study is in the presence of a high dose of captopril which should inhibit approximately 13% conversion to angiotensin II by angiotensin converting enzyme (ACE) (Lembeck, Griesbacher, & Eckhardt, 1990) and block its action, but this was not the case. Indeed using colonic tissue from control rats, the contractile activity of angiotensin I could not be prevented by using inhibitors of other potential angiotensin I to angiotensin II converting pathways such as chymase by chymostatin (Cernucan et al, 2007;Heuston & Hyland, 2012) and cathepsin A by ebelactone B (Ostrowska et al, 2005) in the presence of captopril that was, however, completely blocked by losartan (Spak, Casselbrant, Olbers, Lonroth, & Fandriks, 2008) (results not shown).…”

Angiotensin-converting enzyme gene polymorphisms and the risk of psoriasis: a meta-analysis

“…A previous study showed that ACE is essential for control of normal extracellular volume and arterial vasoconstriction, and these are affected by expression of the ACE gene, which is located on chromosome 17. An insertion/deletion (I/D) polymorphism has been identified, which generates three genotypes: D/D, I/D and I/I.…”

“…6 Most gene variants involve susceptibility loci, including the various psoriasis susceptibility genes (PSORS1-13), the gene for interleukin 12B and the gene for angiotensin-converting enzyme (ACE). [7][8][9] A previous study showed that ACE is essential for control of normal extracellular volume and arterial vasoconstriction, 10 and these are affected by expression of the ACE gene, which is located on chromosome 17. An insertion/deletion (I/D) polymorphism has been identified, which generates three genotypes: D/D, I/D and I/I.…”

Influence of several peptidase inhibitors on the pro-inflammatory effects of substance P, capsaicin and collagenase

“…However, while ACE inhibitors largely increase bradykinin-induced oedema , used alone, they do not modify plasma exudation induced by SR Similarly, captopril does not affect the vasodilatory effect of SP in hamster cheek pouch (Gao and Rubinstein 1995). In fact, comparatively to bradykinin, SP is a poor substrate for ACE (Skidgel et al 1984;Lembeck et al 1990). In rats, the increase of vascular permeability induced by SP was enhanced by ACE inhibitors in combination with phosphoramidon, a NEP inhibitor, or with diprotin A, a DAP IV inhibitor.…”