Studies on the Mechanism of Pinacidil-Induced Vasodilation
Purohit, Surendar S.
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It has been shown that pinacidil has its vasodilatory effects by increasing the K+ permeability of the smooth muscle cell. Recent work with pinacidil has suggested the presence of a K+ conductance-independent mechanism of action. The purpose of this project was to further investigate pinacidil's K+ conductance-independent mechanism of action using isometric contractions induced by norepinephrine (NE) or 8OmM K+. Pinacidil was found to dose-dependently inhibit the phasic component of HE-induced contractions in the rabbit thoracic aortic artery (RAO) and in the rabbit mesenteric artery (RMA). The action of ryanodine, a drug which some studies suggested disrupts the sarcoplasmic reticulum (SR) function, was confirmed in :this project. In addition, data in this study suggested that ryanodine did not affect the influx of extracellular Ca+ in contractions induced by NE or 8OmM K+. Pinacidil's K+ conductance-independent mechanism in RAO was also verified in this study. It was found that the SR does not seem to play an essential role in pinacidil's K+ conductance independent mechanism of action. From the results, it appears that the K+ conductance-independent mechanism of action of pinacidil may involve the extrusion of Ca+2 from the cell or a direct inhibition of the Ca+2 sensitivity of contractile proteins in the cell.