THIOBARBITURATES SUPPRESS DEPOLARIZATION-INDUCED CONTRACTION OF VASCULAR SMOOTH-MUSCLE WITHOUT SUPPRESSION OF CALCIUM INFLUX

We have studied the effects of barbiturates on vascular smooth muscle tension and cytosolic calcium concentrations ([Ca2+](i)) in endotheliu m-denuded rat aortic rings, preloaded with fluo-3. Changes in [Ca2+](i ) were estimated by the fluorescence intensity of the calcium-bound fo rm of fluo-3. In aortic rings under basal conditions, thiobarbiturates (thiopentone and thiamylal 100-300 mu mol litre(-1)) increased [Ca2+] (i), concomitantly with an increase in tension, although oxybarbiturat es (pentobarbitone and secobarbitone up to 300 mu mol litre(-1)) had n o effect. Thiopentone (300 mu mol litre(1))-induced increases in tensi on 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 KCI (30 mmol litre(-1))-precontracted aortic rings, thiopentone decreased tension without reduction of [Ca2+](i), whereas pentobarbito ne decreased tension and [Ca2+](i). KCl (30 mmol litre(-1))-induced co ntraction was suppressed by pretreatment with all barbiturates (100-30 0 mu mol litre(-1)); thiopentone 300 mu mol litre(-1) suppressed contr action to 64.8 (2.5) % (n=6) and pentobarbitone 300 mu mol litre(-1) t o 57.5 (2.2)% (n=9). However, the increase in [Ca2+](i) was suppressed by oxybarbiturates (pentobarbitone 300 mu mol litre(-1) to 77.9 (5.2) %; n=9), but not altered by thiobarbiturates. These results suggest t hat thiobarbiturates and oxybarbiturates affect vascular smooth muscle differently and that the affected site in thiobarbiturate-induced vas odilatation is distal to regulation of [Ca2+](i).