Vascular effects of 3-carbomethoxypyridine on rabbit aortic smooth muscle

Background: 3-Carbomethoxypyridine (3-CMP) is a methyl nicotinate that has been isolated and characterized from one of the alkaloidal fractions of Pyrenacantha staudtii. No literature is available on its vascular action. The goal of this study was to characterize the mechanism of action of 3-CMP on rabbit aortic smooth muscle. Methods: Isometric contractions of ring segments of rabbit aorta (under an initial load of 2g) suspended in 20ml organ baths containing physiological salt solution (PSS) and bubbled with 95% O2, 5% CO2, were examined at 37oC and pH 7.4. The protocols examined are: Dose response of tissues to phenylephrine (PE), effect of 3-CMP on baseline tension, dose response of tissues to 3-CMP following phenylephrine (PE, 10-7M) or high K+ (40mM) pre-contraction as well as relaxation responses to 3-CMP and Ach in endothelium-intact and endothelium-denuded rings.Results: The results show that 3-CMP dose-dependently attenuated the contractile responses to PE and High K+. The respective maximum relaxation responses to 3-CMP following pre-contractions with PE (n=8) or high K+ (n=9) were 50.06±2.94 and 18.59±2.88 (p<0.05). Ach-induced relaxation was observed only in rings with intact endothelium. Also 3-CMP-induced relaxation responses were significantly attenuated in endothelium-denuded rings. Conclusion: The results suggest that 3-CMP elicits relaxation of rabbit aortic smooth muscle activated by depolarizationdependent (high-K+) or –independent (PE) agents. The greater effect on PE contraction suggests interference with mechanisms involving agonist-receptor interaction. 3-CMP relaxation is also endothelium-dependent.Keywords: 3-Carbomethoxypyridine, Rabbit Aorta,Vascular smooth muscle, Endotheliu