Agents and actions. Supplements最新文献

Non-steroidal antiinflammatory drugs (NSAIDs) are commonly used for the treatment of inflammation, pain, and fever. Mechanistically, these compounds are believed to act via inhibition of the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to the prostaglandins (PGs). Although commercially available NSAIDS are efficacious antiinflammatory agents, significant side effects limit their use. Recently two forms of COX were identified- a constitutively expressed COX-1 and a cytokine-inducible COX-2. Commercially available NSAIDs like indomethacin inhibit both COX-1 and COX-2 suggesting the hypothesis that toxicities associated with NSAID therapy are due to inhibition of the non-regulated or constitutive form of COX (COX-1) in normal tissues, whereas therapeutic benefit derives from inhibition of the inducible enzyme, COX-2, at the site of inflammation. Therefore, a selective inhibitor of COX-2 may be anti-inflammatory without GI toxicity-providing a significant improvement over currently available NSAIDs.

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.

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.

An endogenous NO-release which exceeds the basal endogenous NO-release has a regulatory effect on capillary microvasculature in isolatedly perfused rat hearts. The basal NO-release in contrast has no effect on capillaries. The functional findings are corresponding to the endothelial distribution of NOS in coronary vessels, which displays a lack of NOS in capillary endothelium. An increase of coronary flow by exogenously administered NO-donors does not necessarily lead to a dilation of capillary microvasculature. Local differences in the release of unstable NO by SNP and GTN are responsible for variations in effects. We can conclude: NO influences the dilation of the capillary microvasculature independently of flow regulation.

The effects of PGE1, PGE0 and the stable PGE1-analogue SPM 206 on human epicardial coronary arteries were studied in vitro. The tension of the isolated arterial rings was measured isometrically. After precontraction, concentration-response curves with the compounds were performed. PGE1 and SPM 206 elicited concentration-dependent relaxations which are counteracted by a contractile action in higher concentrations. In PGE0, the contractile action occurred even in lower concentrations. This contraction was antagonized by the selective thromboxane A2 antagonist SQ 29,548, resulting in an equipotent relaxation for all three compounds.