Differential sensitivity to ATP-sensitive potassium channel openers of norepinephrine-induced contraction of guinea pig and rat aorta.
Vasorelaxant effects of ATP-sensitive potassium (K(ATP)) channel openers were examined on the tonic phase of vascular contraction induced by norepinephrine (NE) in guinea pig and rat aorta. K(ATP) channel openers, NIP-121 and cromakalim, produced glibenclamide-sensitive and concentration-dependent relaxations in guinea pig and rat aorta preconstricted with NE. However, the vascular relaxations induced by both K(ATP) channel openers were less pronounced in guinea pig aorta than in rat aorta. D-cis-Diltiazem, at the concentration up to 10(-5) M, did not appreciably inhibit the NE-induced contraction of guinea pig aorta, whereas the compound almost completely inhibited the NE-induced contraction of rat aorta at the same concentration. By contrast, sodium nitroprusside relaxed the NE-induced contractions in both guinea pig and rat aorta with similar potencies. These findings suggest that vasorelaxant effects of K(ATP) channel openers on the NE-induced sustained contraction in guinea pig aorta is not attributable to the subsequent inhibition of Ca2+ influx through L-type voltage-gated Ca2+ channels. Lower sensitivity of guinea pig aortic smooth muscle to K(ATP) channel openers is most likely due to the low dependence of NE-induced contraction on the Ca2+ influx in this vascular smooth muscle.
Saito
W
W
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi-City, Chiba, Japan.
Aida
M
M
Sasaki
M
M
Saito
Y
Y
Tanaka
Y
Y
Tanaka
H
H
Shigenobu
K
K
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D019806:Cromakalim / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists*; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D010069:Oxadiazoles; D010880:Piperidines; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D019806:Cromakalim; C070366:NIP 121; D000255:Adenosine Triphosphate; D004110:Diltiazem; D005905:Glyburide; D009638:Norepinephrine