The Mechanisms Of Vasorelaxation And The Effects On Cardiomyocytes Of Triterpenoid Compounds

OBJECTIVE To investigate the mechanisms and characteristics of the vasorelaxation, and theeffects on cardiomyocytes of the compounds NO.38,24,116,116-1 and 117.METHODS In vitro thoracic aortic strips model, In vitro rat tail model, the other kinds of smoothmuscle model, In vivo normal and hypertensive rat model, and the hypoxia/reoxygenation (H/R) inrat primary cardiomyocytes model In vitro were used in this research.RESULTS (1) Compound NO.24 could shift the concentration-response curves for norepinephrine (NE) to the right (EC50 being larger, P<0.05), and increased maximal response at the dosage of 10μg/ml (P<0.05).(2) In vitro thoracic aortic strips model. The preincubation of arterial strips with NO.38 caused rightward shift of the concentration-response curves for KCl and decrease of maximal response (P <0.05), indicating the noncompetitive antagonistic action of NO.38; Similar results were obtained when the contracting responses were induced by NE, but the maximal response of contraction was sustained; Treatment with NO.38 significantly reduced the Ca²⁺ release from intracellular calcium storage in a concentration-dependent manner (P<0.05), but the influx of extracellular calcium was increased; NO.38 relaxed arterial rings in a concentration-dependent manner under the condition of precontraction induced by NE (10^-7M) in the endothelium-intact strips. Significant difference in NO.38-induced relaxation between the endothelium-intact and the endothelium-denuded strips was observed (P <0.001); Pre-treatment with NOS inhibitor N_ω-Nitro-L-arginine methyl ester hydrocholoride (L-NAME, 10^-4M) also significantly inhibited the relaxation induced by NO.38 (40μg/ml); There was no significant influence on the concentration-response curves for Angiotensin II (Ang II, P>0.05) after addition of NO.38 (10～80μg/ml).