Abstract: 310

EFFECTS OF POTASSIUM CHANNEL INHIBITORS ON ENDOTHELIUM-DEPENDENT RELAXATION OF AORTIC RINGS FROM VIRGIN AND PREGNANT RATS.

Chanterelle Cadorette¹ , Michèle Brochu¹ , Jean St-Louis¹
Laboratoire de pharmacologie vasculaire, Centre de recherche, Hôpital Sainte-Justine, Montréal, Québec, Canada ¹

Pregnancy, in both human and rats, is accompanied by decreased arterial pressure, peripheral resistance and responses to vasoconstrictors. It was proposed that endothelium-dependent relaxation could be implicated in these manifestations of pregnancy through an increased production of nitric oxide or increased activity of its effector mechanisms. Among these, activation of potassium channels was suggested. We investigated the effects of blockade of K_ATP and K_Ca channels on carbachol-induced relaxation in aortic rings of term-pregnant and virgin rats. In phenylephrine (1µM) precontracted aortic rings, carbachol induced a concentration-dependent relaxation that was greater in rings of pregnant than virgin rats. In tissues of the latter, glibenclamide (1µM, K_ATP inhibitor) did not affect the relaxation-response curve to carbachol while TEA (0.5mM, K_Ca inhibitor) significantly reduced sensitivity and maximum relaxation to carbachol. In aorta of pregnant rats, although glibenclamide did not show any effect on responses to carbachol, it increased the reduction induced by TEA of carbachol relaxation. In both groups of aortic rings, inhibition of guanylate cyclase by methylene blue (10µM) totally prevented the carbachol-induced response. It is concluded that activation of K⁺ channels contributed to carbachol endothelium-dependent relaxation but the contribution of K_ATP and K_Ca channels appeared different in tissues of virgin and pregnant rats. Moreover, the activation of K⁺ channels in endothelium-dependent relaxation was shown to be the consequence of a cGMP-mediated mechanism. Furthermore, functional alterations of potassium channels were observed on pregnant rat endothelium-denuded aortic rings.

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