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We have studied the effects of barbiturates on vascular smooth muscle tension and cytosolic calcium concentrations ([Ca2+]i) in endothelium-denuded rat aortic rings, preloaded with fluo-3. Changes in [Ca2+]i were estimated by the fluorescence intensity of the calcium-bound form of fluo-3. In aortic rings under basal conditions, thiobarbiturates (thiopentone and thiamylal 100-300 mumol litre-1) increased [Ca2+]i, concomitantly with an increase in tension, although oxybarbiturates (pentobarbitone and secobarbitone up to 300 mumol litre-1) had no effect. Thiopentone (300 mumol litre-1)-induced increases in tension and fluorescence intensity were mean 25.1 (SD 3.2)% and 55.0 (6.0)%, respectively, of those induced by KCl 30 mmol litre-1 (n = 8, each). In KCl (30 mmol litre-1)-precontracted aortic rings, thiopentone decreased tension without reduction of [Ca2+]i, whereas pentobarbitone decreased tension and [Ca2+]i, KCl (30 mmol litre-1)-induced contraction was suppressed by pretreatment with all barbiturates (100-300 mumol litre-1); thiopentone 300 mumol litre-1 suppressed contraction to 64.8 (2.5)% (n = 6) and pentobarbitone 300 mumol litre-1 to 57.5 (2.2)% (n = 9). However, the increase in [Ca2+]i was suppressed by oxybarbiturates (pentobarbitone 300 mumol litre-1 to 77.9 (5.2) %; n = 9), but not altered by thiobarbiturates. These results suggest that thiobarbiturates and oxybarbiturates affect vascular smooth muscle differently and that the affected site in thiobarbiturate-induced vasodilatation is distal to regulation of [Ca2+]i.

As thiopental (thiopentone) suppresses cyclic GMP (cGMP) formation produced by nitric oxide donor drugs, we have tested if it suppresses cGMP formation and increases vascular tone after induction of calcium-calmodulin-independent nitric oxide synthase (iNOS). Rat aortic rings were treated with Escherichia coli lipopolysaccharide (LPS) 1 microgram ml-1 for 4 h, and the effects of thiopental on tension, cGMP concentrations and nitrite accumulation were determined. Thiopental 0.3 mmol litre-1 reduced the tension of phenylephrine-precontracted aortic rings before LPS treatment, but caused no significant effects on tension in the presence of L-arginine 10 mumol litre-1 after LPS treatment. L-Arginine 1 mumol litre-1 to 1 mmol litre-1 increased concentrations of cGMP in LPS-treated aorta in a concentration-dependent manner. This was reduced by thiopental 0.3-1 mmol litre-1. Treatment with L-arginine 1 mmol litre-1 increased concentrations of nitrite, the end product of nitric oxide; this was not affected by thiopental 1 mmol litre-1. We conclude that thiopental suppressed cGMP formation in iNOS-induced vascular smooth muscle without affecting nitric oxide production.