Endothelium-independent contractions of human cerebral arteries in response to vasopressin.
We studied the effects of vasopressin in isolated segments from branches (500-700 micrograms in external diameter) of human middle cerebral arteries obtained during autopsy of 15 patients who had died 3-8 hours before. Paired segments, one normal and the other de-endothelized by gentle rubbing, were mounted for isometric recording of tension in organ baths. In 11 normal segments, vasopressin produced concentration-dependent contractions with an EC50 of 7.0 X 10(-10) M. Removal of the endothelium from 12 segments did not significantly affect vasopressin-induced contractions. Vasopressin produced further contractions in arterial segments with (n = 4) or without (n = 5) endothelium precontracted with KCl. In segments precontracted with prostaglandin F2 alpha, acetylcholine choline caused relaxation only of those with endothelium. At 10(-8) M (n = 11), the vasopressin V-1 receptor antagonist d(CH2)5Tyr(Me)AVP produced a 60-fold shift to the right of the control response curve for vasopressin. Increasing the concentration of the receptor antagonist to 10(-6) M (n = 7) further displaced the control curve in a parallel manner. These results indicate that vasopressin exerts a powerful constrictor action on isolated human cerebral arteries by direct stimulation of V-1 receptors located predominantly on smooth muscle cells. It appears that this contractile response is not modulated by the presence of an intact endothelial cell layer.
Martín de Aguilera
E
E
Departamento de Fisiología, Universidad de Valencia, Spain.
Vila
J M
JM
Irurzun
A
A
Martínez
M C
MC
Martínez Cuesta
M A
MA
Lluch
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011189:Potassium Chloride / Q000494:pharmacology; D014661:Vasoconstriction; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D014667:Vasopressins; D001127:Arginine Vasopressin; D011189:Potassium Chloride; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D000109:Acetylcholine