Role of endothelium in angiotensin II formation by the rat aorta and mesenteric arterial bed

Leite, Rômulo; Estevão, Rodrigo Augusto Fernandes; Resende, Ângela Castro; Salgado, Maria Cristina O.

doi:10.1590/s0100-879x1997000500013

Cited by 13 publications

(12 citation statements)

References 31 publications

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“…However, endothelial removal did not alter the effects of AT 1 R blockade on vasoconstriction suggesting that the endothelium is not necessary for vascular Ang II formation. In agreement with these observations, Leite et al 49 found that endothelium-denuded mesenteric arteries were still able to produce Ang II.…”

Section: Arenas Et Al Tnf-␣ and Vascular Ang II In Estrogen Deficiencmentioning

confidence: 55%

Tumor Necrosis Factor-α and Vascular Angiotensin II in Estrogen-Deficient Rats

Arenas

Armstrong

et al. 2006

Hypertension

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Abstract-Alterations in the vascular angiotensin II system may play a role in the pathophysiology of vascular disease after menopause. In previous studies we have shown that an increase in tumor necrosis factor (TNF)-␣ levels in aging rats because of estrogen deficiency may result in vascular dysfunction. In this study we investigated the effect of TNF-␣ inhibition in angiotensin II modulation of vascular function in aging female animals. Female rats approaching reproductive senescence (12 to 15 months old) were ovariectomized and treated with placebo, estrogen, or a selective TNF-␣ inhibitor (etanercept) for 4 weeks. Expression of angiotensin II in mesenteric arteries was evaluated by immunofluorescence, and the expression of angiotensin-converting enzyme and angiotensin type I receptor (AT 1 R) was investigated by Western immunoblot. Vascular function was assessed in mesenteric arteries using the myograph system, and the role of endogenous angiotensin II on adrenergic vasoconstriction was evaluated in vitro by selective AT 1 R blockade (Candesartan; 10 mol/L). Our data demonstrate that estrogen-depleted rats have higher serum levels of TNF-␣ and greater sensitivity to phenylephrine vasoconstriction compared with estrogen-replaced animals, which was attenuated by AT 1 R blockade. In vivo TNF-␣ inhibition or estrogen replacement reduced phenylephrine constriction of mesenteric arteries and decreased the modulation of this vasoconstriction by candesartan. These functional changes were accompanied by a reduction in the vascular expression of angiotensin II, angiotensin-converting enzyme, and AT 1 R.

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Section: Arenas Et Al Tnf-␣ and Vascular Ang II In Estrogen Deficiencmentioning

confidence: 55%

Tumor Necrosis Factor-α and Vascular Angiotensin II in Estrogen-Deficient Rats

Arenas

Armstrong

et al. 2006

Hypertension

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“…Although AngII formation in rodents is primarily ACErelated (2), non-ACE-dependent AngII formation has also been observed in rat heart (34) and vasculature (35,36). Guo et al (36) demonstrated that chymase expression and chymostatininhibitable ACE activity were significantly increased in spontaneously hypertensive rats, suggesting a possible role for this enzyme in AngII formation in rats.…”

Section: Discussionmentioning

confidence: 99%

Renal Interstitial Fluid Angiotensin I and Angiotensin II Concentrations during Local Angiotensin-Converting Enzyme Inhibition

Nishiyama

Seth²,

Navar³

2002

Journal of the American Society of Nephrology

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Abstract. It was recently demonstrated that angiotensin II (AngII) concentrations in the renal interstitial fluid (RIF) of anesthetized rats were in the nanomolar range and were not reduced by intra-arterial infusion of an angiotensin-converting enzyme (ACE) inhibitor (enalaprilat). This study was performed to determine changes in RIF AngI and AngII concentrations during interstitial administration of ACE inhibitors (enalaprilat and perindoprilat). Studies were also performed to determine the effects of enalaprilat on the de novo formation of RIF AngII elicited by interstitial infusion of AngI. Microdialysis probes (cut-off point, 30,000 D) were implanted in the renal cortex of anesthetized rats and were perfused at 2 l/min. The effluent dialysate concentrations of AngI and AngII were measured by RIA, and reported values were corrected for the equilibrium rates at this perfusion rate. Basal RIF AngI (0.74 Ϯ 0.05 nM) and AngII (3.30 Ϯ 0.17 nM) concentrations were much higher than plasma AngI and AngII concentrations (0.15 Ϯ 0

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“…The finding that captopril does not completely block the synthesis of ANG II in endothelial cells (25,57) suggests the existence of non-ACE pathways for ANG II formation and raises the question as to whether ACE is the sole enzyme responsible for ANG II generation in endothelial cells. Indeed, the existence of alternative ANG II-forming pathways in the vascular wall has been reported (17,25,26,31,32,40,42,44,58,60,65).…”

mentioning

confidence: 99%

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

Santos

Caprio²,

Oliveira³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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. Functional role, cellular source, and tissue distribution of rat elastase-2, an angiotensin II-forming enzyme. Am J Physiol Heart Circ Physiol 285: H775-H783, 2003. First published April 24, 2003 10.1152/ajpheart.00818. 2002We recently described a chymostatin-sensitive elastase-2 as the major angiotensin (ANG) II-forming enzyme in the perfusate of the rat mesenteric arterial bed (MAB) with the same cDNA sequence as rat pancreatic elastase-2. The role of this enzyme in generating ANG II was examined in the rat isolated and perfused MAB. The vasoconstrictor effect elicited by ANG I and the renin substrate tetradecapeptide was only partially inhibited by captopril but abolished by the combination of captopril and chymostatin or N-acetyl-AlaAla-Pro-Leu-chloromethylketone (Ac-AAPL-CK; inhibitor originally developed for human elastase-2). The effect induced by [Pro 11 ,D-Ala 12 ]-ANG I, an ANG I-converting enzyme (ACE)-resistant biologically inactive precursor of ANG II, was blocked by chymostatin or Ac-AAPL-CK. It was also demonstrated that cultured rat mesenteric endothelial cells synthesize elastase-2 and that mRNA for this enzyme can be detected in different rat tissues such as the pancreas, MAB, lung, heart, kidney, liver, and spleen. In conclusion, the demonstration of a functional alternative pathway to ACE for ANG II generation in the rat MAB and the fact that cultured MAB endothelial cells are capable of producing and secreting elastase-2 represent strong evidence of a physiological role for this enzyme in the rat vasculature. endothelium; chymostatin SEVERAL STUDIES HAVE POSTULATED the existence of alternative pathways to angiotensin (ANG)-converting enzyme (ACE) for ANG II generation in tissues of different species based on evidence derived from experiments carried out with a combination of protease inhibitors and ANG II receptor antagonists. In a pioneering study (9) in this area, it was demonstrated that the vasoconstrictor response induced by ANG I in blood vessels of the hamster cheek pouch was blocked only partially by ACE inhibitors but completely abolished by ANG II receptor antagonists, leading to the conclusion that this vascular bed converts significant amounts of ANG I to ANG II by a route that does not involve ACE. 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 seve...

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Role of endothelium in angiotensin II formation by the rat aorta and mesenteric arterial bed

Cited by 13 publications

References 31 publications

Tumor Necrosis Factor-α and Vascular Angiotensin II in Estrogen-Deficient Rats

Tumor Necrosis Factor-α and Vascular Angiotensin II in Estrogen-Deficient Rats

Renal Interstitial Fluid Angiotensin I and Angiotensin II Concentrations during Local Angiotensin-Converting Enzyme Inhibition

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

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