Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

Abstract Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involvedwith cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was toinvestigate whether the direct application of 10 –9 –10 –5 M clobenzorex on isolated phenylephrine-precontracted rat aortic ringsproduces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10 –7.5 –10 5 M). The present outcome was not modified by 10 –6 Matropine (an antagonist of muscarinic acetylcholine receptors), 3.1 +10 –7 M glibenclamide (an ATP-sensitive K channelblocker), 10 –3 M 4-aminopyridine (4-AP; a voltage-activated K + channel blocker), 10 –5 M indomethacin (a prostaglandinsynthesis inhibitor), 10 –5 M clotrimazole (a cytochrome P450 inhibitor) or 10 M cycloheximide (a general protein synthesisinhibitor). Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (Po0.05) by 10