Effects of niflumic acid on alpha1-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 microM), 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 alpha1-adrenoceptor-mediated vasoconstriction in mesenteric blood vessels. In addition, the contribution of chloride ions in alpha1-adrenoceptor-mediated vasoconstriction in blood vessels from hypertensive rats appears to be reduced.
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Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
Tabrizchi
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D000316:Adrenergic alpha-Agonists / Q000009:adverse effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000139:chemically induced / Q000503:physiopathology*; D007093:Imidazoles / Q000009:adverse effects; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009544:Niflumic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D018340:Receptors, Adrenergic, alpha-1; D009544:Niflumic Acid; D012083:Renin; C014282:cirazoline