Rosuvastatin-induced responses in calf cardiac vein.

Abstract

The effects of Rho-kinase inhibitors on vasodilatation induced by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor rosuvastatin (10-9-10-4M) on 5-HT-precontracted calf cardiac vein and the role of endothelium in these effects were analyzed. Cardiac vein ring preparations were suspended in organ baths containing 25 ml of Krebs-Henseleit solution, maintained at 37 °C and continuously gassed with 95% O2-5% CO2. At the end of the resting period, the cardiac vein preparations were contracted with 10(-6) M 5-HT. After the contraction had reached a steady state, rosuvastatin was added to the organ bath cumulatively (10(-9)-10(-4) M). Rosuvastatin relaxed the cardiac vein rings in general while the degree of relaxation was greater in those with endothelium and lower in those without it. HA1077 [1-(5-isoquinolinesulfonyl)-homopiperazine] (Fasudil, 10(-6) M) and Y-27632 [(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide dihydrochloride] (10(-6) M) incubation increased the rosuvastatin-induced relaxation only in the presence of endothelium. The results demonstrate for the first time that in calf cardiac vein, rosuvastatin induced endothelium-dependent relaxations while Rho-kinase inhibition increased these relaxations in the presence of endothelium layer (Fig. 3, Ref. 44).