Relaxant effects of pravastatin, atorvastatin and cerivastatin on isolated rat aortic rings

Increasing evidence suggests that statins may have pleiotropic effects on vascular wall independent of their cholesterol lowering properties. In the present study, we investigated the acute vascular effects of pravastatin, atorvastatin and cerivastatin on rat isolated aortic rings. Statins effectively and comparably relaxed the aortic rings precontracted submaximally with noradrenaline, in a concentration-dependent manner, in which a high potency was observed with cerivastatin. Endothelium removal or incubation of the aortic rings with nitric oxide synthase inhibitor L-NOARG (10(-4) M) and/or cyclooxygenase inhibitor indomethacin (10(-5) M) significantly attenuated the acute vasorelaxation induced by either of statin. Additionally, different from the other two statins, a significant reduction was observed in response to cerivastatin in the presence of K-ATP channel inhibitor, glibenclamide (10(-5) M) and Na+-K+ ATPase inhibitor, ouabain (10(-4) M). Furthermore, pretreatment of the rings with the cholesterol precursor mevalonate (10(-3) M) significantly inhibited the endothelium-mediated relaxant effects of the statins. Our findings suggest that statins could acutely modulate vascular tone importantly by endothelium-dependent and mevalonate-related pathways. (C) 2004 Elsevier Inc. All rights reserved

Synthesis and evaluation of antimicrobial and anticonvulsant activities of some new 3-[2-(5-aryl-1,3,4-oxadiazol-2-yl/4-carbethoxy-methylthiazol-2-yl)imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-ones and investigation of their structure-activity relationships

In the present study, 20 new compounds having 3-[2-(5-aryl-1,3,4-oxadiazol-2-yl] imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-one (I-XII) and 3-[2-(4-carbetboxymethylthiazol-2-yl)imino-4-thiazolidinon-5- ylidene] -5-substituted/nonsubstituted 1H-indole-2-one (XIII-W systems were synthesized. The structures were confirmed by spectral methods (UV, IR, H-1-NMR, C-13-NMR, C-13-DEPT (135), electron impact mass spectrometry) and elemental analysis. All compounds were tested for in vitro antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis ATCC 14153, Candida albicans ATCC 10231, Microsporum gypseum (NCPF-580), Microsporum canis, Trichophyton mentagrophytes and Trichophyton rubrum and some of them were found to be active. Especially, compound I was more active than cefuroxime sodium (CAS 56238-63-2) which was used as a standard, and the activity of compound XII was close to that of cefuroxime sodium against Staphylococcus epidermidis ATCC 12228. Primary screening for antituberculous activity was conducted at 6.25 mu g/ml against Mycobacterium tuberculosis H37Rv in BACTEC 12B medium using the BACTEC 460 radiometric system. The anticonvulsant activities of selected prototoype compounds (I, IV-VI, VIII, XI, XIII, XVI-XVIII) administered at doses of 50-200 mg/kg (i.p.) were evaluated using the pentetrazol test (PTZ) in mice

Comparative effects of tolazoline and nitroprusside on human isolated radial artery

Background. The radial artery is increasingly being used in coronary revascularization as an alternative conduit to a saphenous vein graft. Its perfect endothelial capacity provides a high patency rate comparable with the internal mammary artery (IMA). However, its spastic characteristics cause difficulties during its intraoperative preparation and may lead to early postoperative graft failure. Thus, treatment and/or prevention of radial artery spasm with an effective vasodilator agent is essential for its longevity. Endogenous vasoconstrictors, including noradrenaline, endothelin-1, and thromboxane A, are likely to play a role in the pathogenesis of graft spasm. In the present study, we evaluated the vasorelaxant effect of tolazoline, a nonselective alpha-adrenoceptor blocker, against the contractions induced by various spasmogenic agents in an isolated human radial artery