Thiopental inhibits nitric oxide production in rat aorta

We studied whether thiopental affects endothelial nitric oxide dependent va sodilator responses and nitrite production (an indicator of nitric oxide pr oduction) elicited by acetylcholine, histamine, and A23187 in rat aorta (ar tery in which nitric oxide is the main endothelial relaxant factor). In add ition, we evaluated the barbiturate effect on nitric oxide synthase (NOS) a ctivity in both rat aorta and kidney homogenates. Thiopental (10-100 mu g/m L) reversibly inhibited the endothelium-dependent relaxation elicited by ac etylcholine, histamine, and A23187. On the contrary, this anesthetic did no t modify the endothelium-independent but cGMP-dependent relaxation elicited by sodium nitroprusside (1 nM - 1 mu M) and nitroglycerin (1 nM - 1 mu M), thus excluding an effect of thiopental on guanylate cyclase of vascular sm ooth muscle. Thiopental (100 mu g/mL) inhibited both basal (87.8 +/- 14.3%) and acetylcholine- or A23187-stimulated (78.6 +/- 3.9 and 39.7 +/- 5.6%, r espectively) production of nitrites in aortic rings. In addition the barbit urate inhibited (100 mu g/mL) the NOS (45 +/- 4 and 42.8 +/- 9%) in aortic and kidney homogenates, respectively (measured as C-14-labeled citrulline p roduction). In conclusion, thiopental inhibition of endothelium-dependent r elaxation and nitrite production in aortic rings strongly suggests an inhib itory effect on NOS. Thiopental inhibition of the NOS provides further supp ort to this contention.