Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The heptapeptide, angiotensin-(1-7), is an active member of the renin-angiotensin system. The present study was designed to characterize the role of endothelium in relaxations of large cerebral arteries to angiotensin-(1-7). Rings of canine middle cerebral arteries were suspended in organ chambers for isometric force recording. The levels of cyclic guanosine 3',5'-monophosphate (cGMP) were assessed by radioimmunoassay. During contraction to uridine 5'-triphosphate (UTP, 3x10(-6) to 10(-5) mol/l), angiotensin-(1-7) (10(-9) to 3x10(-5) mol/l) caused concentration-dependent relaxations in arteries with endothelium, but not in endothelium-denuded vessels. Angiotensin-(1-7) significantly increased formation of cGMP. Nitric oxide synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME, 3x10(-4) mol/l), and selective soluble guanylate cyclase inhibitor, 1 H-[1,2, 4]oxadiazolo[4,3-a]quinozalin-1-one (ODQ, 3x10(-6) mol/l), abolished angiotensin-(1-7)-induced relaxations. Angiotensin receptor antagonists, losartan (10(-5) mol/l), PD 123319 (10(-5) mol/l), [Sar(1),Thr(8)]-angiotensin II (10(-5) mol/l) [Sar(1),Val(5), Ala(8)]-angiotensin II (10(-5) mol/l) or [7-D-Ala]-angiotensin 1-7 (10(-6) mol/l) did not affect these relaxations. However, angiotensin-converting enzyme inhibitor, captopril (10(-5) mol/l) augmented relaxations to angiotensin-(1-7). Finally, bradykinin B(2) receptor antagonist, [D-Arg(0),Hyp(3),Thi(5),D-Tic(7), Oic(8)]-bradykinin (HOE 140, 5x10(-8) mol/l) significantly reduced the effect of angiotensin-(1-7), while bradykinin B(1) receptor antagonist, des-Arg(9), [Leu(8)]-bradykinin (6x10(-9) mol/l) did not influence the vascular response to the heptapeptide. These findings indicate that (1) angiotensin-(1-7) produces relaxation of canine middle cerebral arteries by the release of nitric oxide from endothelial cells, (2) angiotensin receptors do not mediate endothelium-dependent relaxations to the heptapeptide, and (3) this effect appears to be dependent on activation of local production of kinins. Our studies support the concept that angiotensin-(1-7), as a natural vasodilator hormone, may counterbalance the hemodynamic actions of angiotensin II.
 ...
PMID:Angiotensin-(1-7) causes endothelium-dependent relaxation in canine middle cerebral artery. 1091 12

Angiotensin converting enzyme (ACE) inhibitors inhibit both the formation of angiotensin II and the catabolism of bradykinin (BK). They prevent not only hypertension but also cardiac hypertrophy and fibrosis. An increase in BK level stimulates the expression of nitric oxide (NO) synthase (NOS) and induces prostaglandins, both of which are powerful vasodilator factors. The direct effect of BK against cardiac hypertrophy is still unclear. This study was performed to examine the cardioprotective effects of BK in hypertrophic models. Renovascular hypertensive (RHT) rats were treated with BK (1,000 ng/kg/day), BK+D-arginyl-[Hyp(3), Thi(5), D-Tic(7), Oic(8)]-bradykinin (HOE140) (a BK B(2) receptor antagonist), and BK+N(omega)-nitro-L-arginine methyl ester (L-NAME) (a NOS inhibitor) for 3 weeks. Blood pressure was measured and echocardiographic analysis performed during the treatment. Histological data were analyzed to confirm the hypotrophic effect of BK. Treatment with BK improved cardiac remodeling, reducing both the heart weight/body weight ratio and the left ventricular wall thickness. However, co-treatment with HOE140 or L-NAME reversed the anti-hypertrophic action of BK. In particular, cardiac fibrosis or perivascular fibrosis, along with collagen accumulation, were inhibited by treatment with BK, while HOE140 and L-NAME counteracted these changes. In addition, expressions of atrial natriuretic peptides (ANP) and brain natriuretic peptides (BNP), which are markers of cardiac abnormalities, were down-regulated by treatment with BK. These effects were reversed by co-treatment with HOE140 and L-NAME. Together, these results indicate that BK directly inhibits the progression of cardiac hypertrophy and cardiac fibrosis due to NO release via the BK B(2) receptor. The BK-NO pathway may play an important role in the progression of cardiac remodeling.
 ...
PMID:Effects of bradykinin on cardiovascular remodeling in renovascular hypertensive rats. 1582 69

An alcohol-free grape-skin extract (GSE) obtained from skins of Vitis labrusca has significant anti-hypertensive, antioxidant and vasodilator effects. According to our previous results, the vasodilator effect of GSE in the isolated mesenteric vascular bed (MVB) of the rat is dependent on endothelium and partially dependent on nitric oxide (NO). In the MVB of the rat pre-contracted with norepinephrine (NE), bolus injections of GSE induced a long-lasting dose-dependent vasodilation that is significantly reduced after the treatment with 1H-[1,2,3] oxadiazolo [4,4-a] quinoxalin-1-one (ODQ). Additionally, in vessels pre-contracted with norepinephrine and depolarized with KCl (25 mM) or treated with Ca(2+)-dependent K(+)-channel blockers charybdotoxin (ChTx) plus apamin, the vasodilator effect of GSE was significantly reduced and almost abolished by ChTx plus apamin plus L-NAME. However, the vasodilator effect of GSE was unaffected by D-Arg[Hyp(3),Thi(5),D-Tic(7),Oic(8)]bradykinin (HOE-140), atropine, yohimbine, pyrilamine and 4-aminopyridine (4-AP). The vasoconstriction response elicited by bolus injection of KCl was not affected by GSE, whereas the vasoconstrictor response induced by NE was dose-dependently and completed inhibited by GSE in the presence but not in the absence of endothelium. However, NE-induced vasoconstriction in calcium-free condition or without endothelium was not reduced by GSE. The present results demonstrate that GSE induces a vasodilator effect in the rat MVB, which is dependent on NO in combination with endothelium-derived hyperpolarizing factor (EDHF). Additionally, our results indicated that extracellular Ca(2+) has an important role on the endothelium-dependent vasodilator effect induced by GSE.
 ...
PMID:Mechanism of the endothelium-dependent vasodilator effect of an alcohol-free extract obtained from a vinifera grape skin. 1602 62