Analysis of cromakalim-, pinacidil-, and nicorandil-induced relaxation of the 5-hydroxytryptamine precontracted rat isolated basilar artery.
The effects of the K+ channel activators cromakalim, pinacidil, and nicorandil were investigated in endothelium intact, 5-hydroxytryptamine (5-HT) precontracted rat isolated basilar artery. Cromakalim, pinacidil, and nicorandil produced concentration-dependent relaxation of rat isolated basilar artery precontracted with 5-HT with a rank order of potency of cromakalim greater than pinacidil greater than nicorandil. All compounds produced full or nearly full relaxation. The calculated Hill coefficients for cromakalim-, pinacidil-, and nicorandil-induced relaxation of 5-HT-precontracted rat isolated basilar artery were 2.20 +/- 0.36, 1.30 +/- 0.07, and 1.00 +/- 0.01, respectively. Under conditions of increased tone produced by 50 mmol/l KCl (which inhibits cromakalim-induced relaxation) pinacidil and nicorandil produced marked reversal of spasm, with pinacidil being more potent than nicorandil. In arteries precontracted with 5-HT, preincubation with glibenclamide (0.1-1 mumol/l) produced concentration-related inhibition of relaxation with calculated mean pA2 values (and slopes of Schild regression) +/- SEM of 6.84 +/- 0.20 (1.1 +/- 0.20) against cromakalim. 6.60 +/- 0.14 (0.95 +/- 0.23) against nicorandil, and 6.57 +/- 0.26 (1.04 +/- 0.18) against pinacidil. For cromakalim, pinacidil, and nicorandil the slopes of Schild regression were not significantly different from unity. Tolbutamide 10 mumol/l was without effect against the cromakalim-, pinacidil-, or nicorandil-induced relaxation. Tetraethylammonium (TEA; 1-10 mmol/l) produced noncompetitive inhibition of the cromakalim-induced relaxation, but appeared to produce competitive inhibition of the pinacidil- and nicorandil-induced relaxations. We conclude that cromakalim, pinacidil, and nicorandil produce relaxation of the 5-HT precontracted rat basilar artery by similar mechanisms to those identified in other peripheral vascular and visceral smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Ksoll
E
E
Physiologisches Institut, Universität München, Federal Republic of Germany.
Parsons
A A
AA
Mackert
J R
JR
Schilling
L
L
Wahl
M
M
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004347:Drug Interactions; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D012702:Serotonin Antagonists; D014665:Vasodilator Agents; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D012701:Serotonin; D020110:Pinacidil; D005905:Glyburide