Angiotensin II type 1 receptor blockade restores angiotensin-(1–7)-induced coronary vasodilation in hypertrophic rat hearts

2013 ◽  
Vol 125 (9) ◽  
pp. 449-459 ◽  
Author(s):  
Álvaro P. S. Souza ◽  
Deny B. S. Sobrinho ◽  
Jônathas F. Q. Almeida ◽  
Gisele M. M. Alves ◽  
Larissa M. Macedo ◽  
...  

The aim of the present study was to investigate the coronary effects of Ang-(1–7) [angiotensin-(1–7)] in hypertrophic rat hearts. Heart hypertrophy was induced by abdominal aorta CoA (coarctation). Ang-(1–7) and AVE 0991, a non-peptide Mas-receptor agonist, at picomolar concentration, induced a significant vasodilation in hearts from sham-operated rats. These effects were blocked by the Mas receptor antagonist A-779. Pre-treatment with L-NAME (NG-nitro-L-arginine methyl ester) or ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one) [NOS (NO synthase) and soluble guanylate cyclase inhibitors respectively] also abolished the effect of Ang-(1–7) in control hearts. The coronary vasodilation produced by Ang-(1–7) and AVE 0991 was completely blunted in hypertrophic hearts. Chronic oral administration of losartan in CoA rats restored the coronary vasodilation effect of Ang-(1–7). This effect was blocked by A-779 and AT2 receptor (angiotensin II type 2 receptor) antagonist PD123319. Acute pre-incubation with losartan also restored the Ang-(1–7)-induced, but not BK (bradykinin)-induced, coronary vasodilation in hypertrophic hearts. This effect was inhibited by A-779, PD123319 and L-NAME. Chronic treatment with losartan did not change the protein expression of Mas and AT2 receptor and ACE (angiotensin-converting enzyme) and ACE2 in coronary arteries from CoA rats, but induced a slight increase in AT2 receptor in aorta of these animals. Ang-(1–7)-induced relaxation in aortas from sham-operated rats was absent in aortas from CoA rats. In vitro pre-treatment with losartan restored the Ang-(1–7)-induced relaxation in aortic rings of CoA rats, which was blocked by the Mas antagonist A-779 and L-NAME. These data demonstrate that Mas is strongly involved in coronary vasodilation and that AT1 receptor (angiotensin II type 1 receptor) blockade potentiates the vasodilatory effects of Ang-(1–7) in the coronary beds of pressure-overloaded rat hearts through NO-related AT2- and Mas-receptor-dependent mechanisms. These data suggest the association of Ang-(1–7) and AT1 receptor antagonists as a potential therapeutic avenue for coronary artery diseases.

2001 ◽  
Vol 19 (6) ◽  
pp. 1121-1129 ◽  
Author(s):  
Rohit Moudgil ◽  
Vijayan Menon ◽  
Yi Xu ◽  
Sorin Musat-Marcu ◽  
Dinender Kumar ◽  
...  

2009 ◽  
Vol 111 (3) ◽  
pp. 227-234 ◽  
Author(s):  
Mohiuddin Ahmed Bhuiyan ◽  
Murad Hossain ◽  
Shin-ichiro Miura ◽  
Takashi Nakamura ◽  
Masanobu Ozaki ◽  
...  

2002 ◽  
Vol 87 (3) ◽  
pp. 327-333 ◽  
Author(s):  
J. Vág ◽  
Beáta Kerémi ◽  
Csilla Hably ◽  
J. Bartha ◽  
Á. Fazekas

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3319-3324 ◽  
Author(s):  
Kathryn M. Gauthier ◽  
David X. Zhang ◽  
Erik M. Edwards ◽  
Blythe Holmes ◽  
William B. Campbell

Abstract Adrenal steroidogenesis is modulated by humoral and neuronal factors and blood flow. Angiotensin II (AII) stimulates adrenal cortical aldosterone and cortisol production and medullary catecholamine release. However, AII regulation of adrenal vascular tone has not been characterized. We examined the effect of AII on diameters of cannulated bovine adrenal cortical arteries. Cortical arteries (average internal diameter = 230 μm) were constricted with U46619 and concentration-diameter responses to AII (10−13 to 10−8 mol/liter) were measured. In endothelium-intact arteries, AII induced dilations at low concentrations (maximum dilation = 25 ± 6% at 10−10 mol/liter) and constrictions at high concentrations (maximum constriction = 25 ± 18% at 10−8 mol/liter). AII constrictions were blocked by the angiotensin type 1 (AT1) receptor antagonist, losartan (10−6 mol/liter). AII dilations were enhanced by losartan (maximal dilation = 48 ± 8%), abolished by endothelial cell removal or N-nitro-l-arginine (L-NA, 3 × 10−5 mol/liter) and inhibited by the angiotensin type 2 (AT2) receptor antagonist, PD123319 (10−6 mol/liter, maximal dilation = 18 ± 4%). In a 4,5-diaminofluorescein diacetate nitric oxide (NO) assay of isolated cortical arteries, AII stimulated NO production, which was abolished by PD123319, L-NA, or endothelial cell removal. Western immunoblot of arterial homogenates and endothelial and zona glomerulosa cell lysates revealed 48-kD and 50-kD bands corresponding to AT1 and AT2 receptors, respectively, in all three and a 140-kD band corresponding to endothelial NO synthase in endothelial cells and arteries. Our results demonstrate that AII stimulates adrenal cortical arterial dilation through endothelial cell AT2 receptor activation and NO release and AT1 receptor-dependent constriction.


2000 ◽  
Vol 23 (2) ◽  
pp. 174-181 ◽  
Author(s):  
Tomoko TOKIOKA ◽  
Masayuki SHIBASAKI ◽  
Akira FUJIMORI ◽  
Yasuko MATSUDA-SATOH ◽  
Wataru UCHIDA ◽  
...  

PLoS ONE ◽  
2011 ◽  
Vol 6 (8) ◽  
pp. e23411 ◽  
Author(s):  
Els Moltzer ◽  
Luuk te Riet ◽  
Sigrid M. A. Swagemakers ◽  
Paula M. van Heijningen ◽  
Marcel Vermeij ◽  
...  

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