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)

A brief review is given of the vasodilators that require an intact vascular endothelium to exert their relaxing effect. Then some major issues of the phenomenon of endothelium-dependent smooth muscle relaxation are discussed in more detail: The chemical structure of the endothelium-derived relaxing factor (EDRF), which mediates this type of vasodilation, is still unclear. There is agreement that EDRF is chemically unstable, but determinations of its biological half-life have yielded discrepant values (6-50 s). Recent evidence suggests that oxygen and/or activated oxygen species accelerate the evanescence of the factor. The biochemical mechanisms involved in the production of EDRF are still largely unknown. Both stimulators of phospholipase A2 and inhibitors of lysolecithin acyltransferase were found to induce EDRF-mediated relaxation, while several phospholipase inhibitors block these relaxations. These findings suggest that cleavage of phospholipids (and formation of free fatty acids and lysophosphatides) play an important role in EDRF production. EDRF-mediated relaxations are associated with increased levels of cyclic GMP in vascular smooth muscle cells. Endothelial cells were found to produce a factor that directly stimulates the enzymatic activity of soluble guanylate cyclase. This stimulating factor is likely to be identical with EDRF. The significance of the endothelium-dependent relaxing mechanism in resistance vessels is still largely unclear. In the blood-perfused hind limb of the rabbit, two irreversible inhibitors of endothelium-dependent vasodilation (gossypol and p-bromophenacyl-bromide) blocked the vasodilation induced by the endothelium-dependent agent acetylcholine, but not the response to the endothelium-independent vasodilator prostaglandin E1.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Properties and mechanisms of production and action of endothelium-derived relaxing factor. 243 90

Vascular endothelium is not only a mechanical, non-thrombogenetic barrier in the blood vessel wall, but probably plays a substantial role in the regulation of vascular smooth muscle tone. Besides the ability to metabolize vasoactive compounds like catecholamines and angiotensins, endothelial cells possess an active biochemical machinery for the production of vasoactive compounds (e.g. prostacyclin). During recent years it has become apparent that a large variety of vasodilator compounds require intact endothelial cells to exert their relaxing action. These endothelium-dependent relaxations are not mediated by prostacyclin of endothelial origin, but by an unknown substance that is referred to as endothelium-derived relaxing factor (EDRF). EDRF is a chemically unstable humoral substance and has a biological half-life in the range of seconds. Although EDRF is not a prostaglandin or leukotriene, several findings suggest possible relationships of its production with the eicosanoid system. Both stimulation of phospholipase A2 and inhibition of lysolecithin acyltransferase induce the production of EDRF. This suggests that cleavage of phospholipids may be an important step in the formation of EDRF. EDRF-mediated vascular relaxations (like relaxations induced by nitrovasodilators) were found to be associated with increases in cyclic GMP in vascular smooth muscle. Endothelial cells produce a factor that directly stimulates the enzymatic activity of soluble guanylate cyclase. Several points of evidence indicate that this factor may be identical with EDRF. Thus the mechanism of action of the EDRF formed endogenously may be similar to that of nitrovasodilators.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Significance of endothelial cells for the regulation of the tone of smooth muscle--formation of an endothelial, relaxing factor]. 287 41