Relaxation of rat aorta by farrerol correlates with potency to reduce intracellular calcium of VSMCs.

Farrerol, isolated from Rhododendron dauricum L., has been proven to be an important multifunctional physiologically active component, but its vasoactive mechanism is not clear. The present study was performed to observe the vasoactive effects of farrerol on rat aorta and to investigate the possible underlying mechanisms. Isolated aortic rings of rat were mounted in an organ bath system and the myogenic effects stimulated by farrerol were studied. Intracellular Ca2+ ([Ca2+]in) was measured by molecular probe fluo-4-AM and the activities of L-type voltage-gated Ca2+ channels (LVGC) were studied with whole-cell patch clamp in cultured vascular smooth muscle cells (VSMCs). The results showed that farrerol significantly induced dose-dependent relaxation on aortic rings, while this vasorelaxation was not affected by NG-nitro-l-arginine methylester ester or endothelium denudation. In endothelium-denuded aortas, farrerol also reduced Ca2+-induced contraction on the basis of the stable contraction induced by KCl or phenylephrine (PE) in Ca2+-free solution. Moreover, after incubation with verapamil, farrerol can induce relaxation in endothelium-denuded aortas precontracted by PE, and this effect can be enhanced by ruthenium red, but not by heparin. With laser scanning confocal microscopy method, the farrerol-induced decline of [Ca2+]in in cultured VSMCs was observed. Furthermore, we found that farrerol could suppress Ca2+ influx via LVGC by patch clamp technology. These findings suggested that farrerol can regulate the vascular tension and could be developed as a practicable vasorelaxation drug.

Diverse effects of L-arginine on cardiac function of rats subjected to myocardial ischemia and reperfusion in vivo.

In vivo administration of L-arginine at different time points during the course of myocardial ischemia and reperfusion (MI/R) has been shown to differentially regulate postischemic apoptosis. Cardiac function is one of the most important indexes used to judge the degree of myocardial injury. The present study attempted to determine whether in vivo administration of L-arginine at different stages of MI/R has a diverse influence on cardiac function of ischemic reperfused hearts and, if so, to investigate the mechanisms involved. Male adult rats were subjected to 30 min myocardial ischemia followed by 5 h reperfusion. An intravenous L-arginine bolus was given either 10 min before and 50 min after reperfusion (early treatment) or 3 h and 4 h after reperfusion (late treatment). Early treatment with L-arginine markedly increased the left ventricular systolic pressure (LVSP) and dP/dt(max), and decreased myocardial nitrotyrosine content. In strict contrast, late treatment with L-arginine resulted in a significant decrease in LVSP and dP/dt(max) from 4 h to 5 h after reperfusion, and increase in toxic peroxynitrite formation as measured by nitrotyrosine. These results suggest that the administration of L-arginine at different time points during the course of MI/R leads to diverse effects on cardiac dysfunction. Early supplementation decreased the nitrative stress and improved left ventricular function. However, late treatment with L-arginine increased the formation of peroxynitrite and aggravated cardiac functional injury.