Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atrial natriuretic peptide (ANP) is secreted by the heart in response mainly to atrial distension and circulates in plasma in picomolar concentrations. It binds to receptors in blood vessels which it relaxes, renal glomeruli where it induces increased glomerular filtration rate, renal papilla to produce natriuresis, adrenal glomerulosa cells to inhibit aldosterone secretion, and median eminence and pituitary where it may inhibit vasopressin secretion. In experimental models of hypertension plasma levels of ANP are uniformly elevated, except in spontaneously hypertensive rats, in which plasma ANP may only rise transiently. The action of ANP on smooth muscle cells of the blood vessel wall results in production of cyclic GMP, which appears to be the second messenger producing relaxation of pre-contracted blood vessels. Mechanisms other than cGMP generation have been proposed but remain unproven as mediators of ANP action. Receptors for ANP in blood vessels are of two subtypes: B-receptors (or R1-receptors), which contain guanylate cyclase in their structure, and C-receptors (or R2-receptors), which have not been shown to the present to be biologically active. Our studies on vascular ANP receptors are reviewed. In several experimental models of hypertension such as saralasin-insensitive 2-kidney, 1-clip and 1-kidney, 1-clip Goldblatt hypertensive rats and in DOCA-salt hypertensive rats, we have found elevated plasma ANP, as well as decreased binding and ANP-induced vascular relaxation and blood pressure-lowering effects of ANP. Both the B and C ANP receptors appear decreased in density, even after acid washing of membranes to remove any retained circulating ANP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vascular receptors for atrial natriuretic peptide in hypertension. 217 36

ANP and NO act via different receptors, although inducing the common intracellular messenger - cyclic GMP. However, interaction between both factors remains unclear. Our observations suggested that in the rat kidney glomeruli, activities of the ANP- and NO-dependent guanylyl cyclase systems may be mutually compensated. To check this, we have tested effects of ANP and sodium nitroprusside (SNP) on cGMP synthesis and relaxation of glomeruli contracted with angiotensin II. The glomeruli were isolated from Wistar rats receiving saline (Control), dexamethasone (DEX), deoxycorticosterone (DOCA) or N-c-nitro-L-arginine methyl ester (NAME) for 1 or 2 days. In the DEX glomeruli exposed to 100 microM SNP, rate of cGMP synthesis was significantly higher then in the Control (26.3 vs 16.0 pmol/mg.prot./2 min., P<0.05), while 1 microM ANP was markedly less effective (2.8 vs 16.7 pmol/mg.prot./2 min in Control, P<0.01). On the contrary, in NAME group 1 microM ANP stimulated cGMP synthesis up to 35.6 pmol/mg.prot./2 min whereas efficacy of SNP was slightly suppressed. High correlation coefficient (r = 0.979, p<0.01) indicates interrelationship between NO- and ANP-dependent cGMP synthesis. Ability of the glomeruli to relax in response to ANP or SNP was in accord to their ability to cGMP generation. This was confirmed by high correlation (r = 0.845, p<0.001) between degree of relaxation and rate of cGMP synthesis. Our results support strongly the hypothesis that both, ANP and NO dependent systems co-operate in regulation of the function of kidney glomeruli.
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PMID:Co-operation between particulate and soluble guanylyl cyclase systems in the rat renal glomeruli. 1101 69

Alpinia zerumbet (K. Schum), a medicinal plant originated from West Asia, is used in the northeast and southeast of Brazil as infusions or decoctions as a diuretic, antihypertensive, and antiulcerogenic. Experiments were undertaken to determine whether a hydroalcoholic extract obtained from leaves of Alpinia zerumbet (AZE) induces vasodilation in the mesenteric vascular bed (MVB), and an antihypertensive effect was also assessed in rats with DOCA-salt hypertension. In MVB precontracted with norepinephrine, AZE induces a long-lasting endothelium-dependent vasodilation that is not reduced by indomethacin. Inhibition of NO synthase by NG-nitro-L-arginine methyl ester (L-NAME) and guanylyl cyclase by 1H-[1,2,3]oxadiazolo [4,4-a]quinoxalin-1-one (ODQ) reduces the vasodilator effect of AZE. In vessels precontracted with norepinephrine, the vasodilator effect of AZE was not changed by 4-aminopyridine, glibenclamide, or by charybdotoxin plus apamin. Concentrations of atropine, pyrilamine, and yohimbine that significantly reduced the vasodilator effect of acetylcholine, histamine, and clonidine, respectively, did not change the vasodilator effect of AZE. HOE 140, which significantly reduced the vasodilator effect of bradykinin, induced a slight but significant reduction on the vasodilator effect of AZE. Chronic oral administration of AZE induced a significant reduction in systolic, mean, and diastolic arterial pressure in rats with DOCA-salt hypertension. Probably the vasodilator effect of AZE is dependent on the activation of the NO-cGMP pathway and independent of activation of ATP-dependent, voltage-dependent, and calcium-dependent K+ channels. Bradykinin receptors may also participate in the vasodilator effect of AZE. Finally, the vasodilator and antihypertensive effects of AZE demonstrated in the present study provide experimental support for the indication of Alpinia zerumbet as an antihypertensive medicinal plant.
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PMID:Antihypertensive and endothelium-dependent vasodilator effects of Alpinia zerumbet, a medicinal plant. 1611 33