Pharmacological effect of endothelin, an endothelium-derived vasoconstrictive peptide, on canine basilar arteries.
The purpose of this study was to evaluate the constrictive effect of endothelin, a peptide vasoconstrictor derived from endothelium, on canine basilar artery. Constriction was measured by an isometric tension recording method. Endothelin induced prolonged contraction of canine basilar artery in a dose-dependent fashion, the estimated concentration at 50% contraction being (2.1 +/- 0.5) X 10(-9) M (mean +/- SEM). Removal of endothelium significantly augmented the arterial response to endothelin. In Ca(++)-free medium no contractile response was elicited at 10(-8) M endothelin. Papaverine (10(-4) M) and nicardipine (10(-8) M), a calcium channel blocker, almost completely inhibited the contraction induced by 10(-8) M endothelin. Pretreatment with nicardipine (10(-8) - 10(-6) M) also significantly suppressed the response to endothelin. Acetylcholine (10(-7) - 10(-4) M), adenosine triphosphate (10(-7) - 10(-5) M), and thrombin (0.1 and 1.0 U/ml) dose-dependently inhibited contraction of canine basilar artery in response to 3 X 10(-9) M endothelin. These results show that endothelin has a potent constrictive effect on canine basilar artery and suggest that this substance may play an important role in the pathogenesis of vasospasm following subarachnoid hemorrhage.
Nakagomi
T
T
Ide
K
K
Yamakawa
K
K
Sasaki
T
T
Kurihara
H
H
Saito
I
I
Takakura
K
K
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects*; D002118:Calcium / Q000502:physiology; D004285:Dogs; D016232:Endothelins; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D010208:Papaverine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D016232:Endothelins; D010455:Peptides; D014662:Vasoconstrictor Agents; D000255:Adenosine Triphosphate; D010208:Papaverine; D002118:Calcium