Effects of niflumic acid on alpha(1)-adrenoceptor-induced vasoconstriction in mesenteric artery in vitro and in vivo in two-kidney one-clip hypertensive rats

The influence of niflumic acid (3 and 10 mu M), a Cl- channel antagonist, on cirazoline-induced vasoconstriction in isolated perfused mesenteric artery (5 ml/min) from two-kidney one-clip (2K1C) hypertensive and sham normotensive rats was examined. In addition, the effect of a single i.v. bolus injection of niflumic acid (3 mg/kg) on cirazoline-mediated reduction in Vascular conductance in superior mesenteric artery was determined in pentobarbital-anaesthetized hypertensive and normotensive rats. Bolus injections of cirazoline induced a dose-dependent transient increase in the perfusion pressure in vitro. In the presence of niflumic acid, cirazoline-mediated vasoconstriction was significantly inhibited. Cirazoline-induced vasoconstriction in isolated mesenteric beds was also significantly inhibited following perfusion with Cl--free buffer. Pre-perfusion of mesenteric blood vessels with Cl--free buffer resulted in a significantly greater inhibition of cirazoline-mediated vasoconstriction in sham normotensive rats than in hypertensive rats. We found that in Cl--free buffer, cirazoline-mediated vasoconstriction could be further inhibited by niflumic acid. Intravenous infusion of cumulative doses of cirazoline in vivo caused a dose-dependent decrease in superior mesenteric vascular conductance. Pretreatment with niflumic acid significantly impaired cirazoline-mediated decreases in Vascular conductance. Our results indicate that chloride ions play an important role in alpha(1)-adrenoceptor-mediated vasoconstriction in mesenteric blood vessels. In addition, the contribution of chloride ions in alpha(1)-adrenoceptor-mediated vasoconstriction in blood vessels from hypertensive rats appears to be reduced. (C) 1997 Elsevier Science B.V.