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)

Recently we demonstrated that the vascular response to angiotensin II (A-II) was attenuated in an endothelium-dependent manner by using the isolated ring specimen iliac arteries of pregnant rabbits. In this paper we investigated the possibility that three vasoactive substances, thromboxane A2(TXA2), prostacyclin (PGI2), and endothelium-derived nitric oxide (EDNO), might be involved in this refractoriness to A-II during pregnancy, by measuring the changes in the vascular response to A-II (pA2, intrinsic activity) of the isolated arterial rings of rabbits before and after the addition of an inhibitor specific for each of these three substances. Sodium ozagrel, TXA2 synthetase inhibitor, decreased the vascular response to A-II more in the blood vessels of pregnant rabbits, regardless of whether the endothelium was intact or denuded, than in the blood vessels of non pregnant rabbits. Tranylcypromine, a PGI2 synthetase inhibitor, significantly increased contractility in the blood vessels with intact endothelium of pregnant rabbits (i.a. = 1.39 +/- 0.099, n = 11, mean +/- SEM), compared to that in the blood vessels with intact endothelium of non pregnant rabbits (i.a. = 1.08 +/- 0.090, n = 7). Methylene blue, a guanylate cyclase inhibitor which blocks the effect of EDNO, amplified the vascular response in blood vessels with intact endothelium of both groups, and more intensely in the blood vessels of pregnant rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of endothelium-derived nitric oxide and prostaglandins on the endothelium-dependent vascular refractoriness to angiotensin II in pregnant rabbits]. 145 44

Interleukin 1 (IL-1) is a pro-inflammatory cytokine which has direct vasorelaxant effects on vascular smooth muscle cells (VSMC). In the present study, IL-1 markedly increased intracellular levels of the vasodilatory mediator, cAMP, in human saphenous and human aortic VSMC. IL-1-induced cAMP was associated with a marked increase in prostacyclin (PGI2) production, and was reversed by indomethacin and tranylcypromine, inhibitors of cyclooxygenase and PGI2 synthetase respectively. Furthermore, PGI2, but not PGE2, was a potent inducer of cAMP production in HSVSMC, implicating a role for PGI2 in mediating IL-1-induced cAMP production. In previous studies, IL-1 increased immunoreactive cGMP production in human saphenous VSMC through a pathway inhibitable by soluble guanylate cyclase inhibitors, methylene blue and LY83583, but not by nitric oxide (NO) synthase inhibitors, suggesting a role of NO-independent activation of soluble guanylate cyclase. However, in the present study, it was found that cAMP cross-reacted significantly in cGMP radioimmunoassays employing three out of four commercial antisera, that IL-1 did not affect cGMP production in human saphenous or human aortic VSMC as determined by an RIA having low cAMP cross-reactivity, and that both LY83583 and methylene blue inhibited IL-1-induced increases in cAMP. The results implicate prostacyclin-dependent cAMP production as a mediator of the vasodilatory effects of IL-1 in humans.
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PMID:Interleukin 1 induces prostacyclin-dependent increases in cyclic AMP production and does not affect cyclic GMP production in human vascular smooth muscle cells. 757 79