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 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.
Kitamura
R
R
Department of Anesthesia, Kyoto University Hospital, Japan.
Kakuyama
M
M
Nakamura
K
K
Miyawaki
I
I
Mori
K
K
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010424:Pentobarbital / Q000494:pharmacology; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012631:Secobarbital / Q000494:pharmacology; D013840:Thiamylal / Q000494:pharmacology; D013858:Thiobarbiturates / Q000494:pharmacology*; D013874:Thiopental / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D018686:Anesthetics, Intravenous; D013858:Thiobarbiturates; D013840:Thiamylal; D012631:Secobarbital; D011189:Potassium Chloride; D010424:Pentobarbital; D013874:Thiopental; D002118:Calcium