Effect of acetylcholine on vascular smooth muscle contraction induced by phenylephrine, angiotensin II and mastoparan-7

Background. The reactivity of blood vessels depends on their structure and the presence of calcium ions. It is modulated by numerous factors which activate specific signalling pathways leading to contraction or relaxation of smooth muscle. The action of various vasodilatation substances may be altered under the influence of similar or quite different modulators. Main aim of this study was to assess the role of acetylcholine and calcium ions in modulating the contraction induced by angiotensin II (ANG II), phenylephrine (PHE) and mastoparan-7, a direct activator of G-protein. Material and methods. Experiments were performed on isolated and perfused tail arteries of Wistar rats. Contraction force in our model was measured by increased level of perfusion pressure with a constant flow. Results. ANG II caused an increase in perfusion pressure in physiological salt solution (PSS) and calcium free PSS (FPSS).Under the influence of increasing concentrations of acetylcholine, a statistically significant reduction in perfusion pressure in both types of fluid was noted. In the presence of nitro-L-arginine (nitric oxide synthase inhibitor, L-NNA) in both solutions, no changes in contraction stimulated by ANG II or spasmolytic effect of acetylcholine were observed. PHE, in a similar manner to ANG II, caused contraction in FPSS and PSS, which was similarly modulated by acetylcholine. In the mastoparan-7 induced contraction, the pattern of tissue response was similar. For all groups, maximal perfusion pressure in PSS was higher than for FPSS. Conclusions. The results of our experiments suggest that acetylcholine by activation of vascular endothelium is able to induce dose-dependent vasodilatation not only in contraction related to typical metabotropic receptor agonists, but also after direct stimulation of G-protein with mastoparan-7. This effect may be reversed in the presence of inhibitors of endothelial synthase of nitric oxide