Nephrotoxicity of acyclovir and ganciclovir in rats: evaluation of glomerular hemodynamics

Effects of pretreatment with thiopental on endothelium-dependent vasodilator responses elicited by drugs in rat aortic rings were investigated. The vasodilators employed were acetylcholine and histamine (endothelium- and receptor-dependent), A23187 (endothelium-dependent but receptor-independent) and sodium nitroprusside (endothelium-independent); they were tested 15 or 60 min after aortic preparations were exposed during 15 min to thiopental. Pretreatment with the barbiturate reversibly inhibited relaxation elicited by either acetylcholine and histamine, but a high concentration of the anesthetic was needed (3.1 mg/ml). On the contrary, thiopental did not modify the relaxation elicited by sodium nitroprusside or A23187. In addition, the barbiturate inhibited basal and acetylcholine-stimulated production of nitrites (an indicator of nitric oxide output) in aortic rings. In conclusion, thiopental inhibited the endothelium-dependent relaxation elicited by either acetylcholine or histamine. Although the barbiturate also inhibited nitric oxide production, the reduction in the relaxant response provoked by it does not seem to be the result of direct guanylate cyclase or nitric oxide synthase alterations, since thiopental did not modify the effect of sodium nitroprusside or A23187. Disturbances elicited by thiopental on endothelial receptors or on signal transduction elements may indirectly provoke nitric oxide synthase inhibition.