Agents and actions. Supplements最新文献

L-arginine (L-Arg) was administered intravenously through 4 consecutive days to 20 males (40-63 years old) with essential hypertension (EH). Significant decrease (p < 0.02) of systolic blood pressure (SBP) was observed only during the first day of the therapy and tachyphylaxis against L-Arg was noticed. The reduction of diastolic blood pressure (DBP) was more marked (p < 0.001). Significant changes in cGMP plasma level and the nitrite/nitrate urine concentration were not observed. L-Arg caused a significant activation of fibrinolysis (p < 0.005). The decrease of platelet activity, measured by the ADP-induced aggregation, after L-Arg administration was not statistically significant. Therefore, L-Arg may play only a secondary role in the treatment of EH.

Studies in isolated smooth muscles and single cells of coronary arteries have demonstrated that both hypoxia and platelet activating factor (PAF) in a similar manner increased contractile force and Ca-activated K currents. The specific antagonists of PAF receptors BN 52021 and WEB 2886 significantly decreased contractile responses of vascular smooth muscle (VSM) to PAF and hypoxia. Taken together, these data allow to suggest that endogenous PAF can produce both phasic and tonic contraction in coronary arteries under hypoxic condition.

Several integrin alpha subunits have structural variants that are identical in their extracellular and transmembrane domains but that differ in their cytoplasmic domains. In the present study, we examined the possibility that the A and B variants of the alpha 6 beta 1 integrin laminin receptor differ in function. P388D1 macrophages that had been transfected with the alpha A integrin subunit were 3-4 fold more migratory than P388D1 macrophages that had been transfected with the alpha 6 B integrin subunit. Deletion of the alpha 6 cytoplasmic domain markedly inhibited the ability of the alpha 6 beta 1 receptor to promote migration.

This study was undertaken to investigate the possible involvement of K+ channels in PGE1-mediated vasodilatation. The increase in coronary flow elicited by PGE1 in isolated working rat hearts was attenuated by phentolamine and glibenclamide, inhibitors of ATP-regulated K+ channels, whereas apamin and charybdotoxin, inhibitors of calcium-activated K+ channels, were ineffective. In the anaesthetized rat, the duration of the hypotensive action of PGE1 was markedly attenuated by glibenclamide. It is concluded that the vasodilatory action of PGE1 in the coronary and systemic circulation of the rat is, at least in part, mediated via an opening of ATP-sensitive K+ channels.

Large amount of nitric oxide (NO) are produced at sites of inflammation through the action of inducible nitric oxide synthase (iNOS) present in both infiltrating leucocytes and activated, resident tissue cells. However, the role of NO in inflammation remains unclear. NO is a vasodilator, which inhibits the adhesion of neutrophils to the vascular endothelium; it reduces the production of IL-6 by Kupffer cells and chondrocytes, and the production of gamma-IFN and TNF-alpha by splenocytes. The literature provides contradictory information on the effect of NO on vascular leakiness, chemotaxis, prostaglandin production and tissue damage. Increasingly, data suggest that NO is immunosuppressive. Inhibitors of NOS have potent prophylactic activity in several but not all, animal models of inflammatory disease. However, in rat adjuvant arthritis, therapeutic activity is weak. Whether inhibitors of iNOS will be therapeutically useful in human inflammatory diseases cannot be predicted on the basis of present information.

Object of our study was to characterize the effects of elevated circulating NO on hemodynamics and vascular smooth muscle cell proliferation in rats. Administration of molsidomine (10, 25, 50 mg/kg, bid p.o.) was followed by pharmacodynamic effects: elevation of plasma nitrite/nitrate levels and reduction of blood pressure (25 and 50 mg/kg, bid p.o.). Under these conditions no antiproliferative activity occurred in a model of "air dried" carotid artery injury. From these results we conclude that NO does not act as an antiproliferative agent under conditions where smooth muscle cell injury predominates.

Prostacyclin is a major vasoprotective molecule. It has multiple physiological functions. Its synthesis is determined by several enzymes of which cyclooxygenase (COX) plays a key role. Two isoforms of COX have been identified. Their expression and regulation are controlled by different mechanisms. COX-1 is constitutively expressed and physiologically important. PGI2 synthesis can be augmented by virus-mediated transfer COX-1 gene. This strategy may be useful for therapy of vascular thrombosis and tissue ischemia.