Characterization of arginine vasopressin actions in human uterine artery: lack of role of the vascular endothelium.
1. The effect of arginine vasopressin (AVP) on human uterine artery rings, both intact and denuded of endothelium, was investigated. 2. Initially, AVP (63 pM-32 nM) induced concentration-dependent contraction of human uterine artery (pD2 = 8.92 +/- 0.01). Removal of the endothelium did not affect the concentration-response curve for AVP (pD2 = 8.83 +/- 0.03). 3. In contrast, human uterine arteries, both intact and denuded of endothelium, did not respond to the addition of 1-desamino-8-D-arginine vasopressin (dDAVP, 1 nM-1 microM). 4. In both types of preparations, [d(CH2)5Tyr(Me)AVP (1-10 nM) and [d(CH2)5,D-Ile2,Ile4]AVP (300 nM-3 microM) produced parallel rightward shifts of the curves for AVP. The Schild plots constrained to a slope of unity gave the following -log KB values: [d(CH2)5Tyr(Me)]AVP vs. [d(CH2)5,D-Ile2,Ile4]AVP 9.66 vs. 6.69 and 9.61 vs. 6.80 for human uterine artery, intact and denuded of endothelium, respectively. 5. The pKA values for AVP itself also did not differ between preparations: 6.56 and 6.43 for human uterine artery with and without endothelium, respectively. In both types of preparations, the receptor reserve (KA/EC50) was considerably greater than unity (intact vs. denuded: 228 vs. 244). 6. It is concluded that, in human uterine artery, AVP induces contractions that are not modulated by the endothelium. It is likely that AVP acts as a full agonist on human uterine artery, regardless of the endothelial condition. On the basis of differential antagonists affinity and affinity of AVP itself, it is probable that vasopressin receptors involved in AVP-induced contraction in human uterine arteries belong to the V1a or V1a-like subtype.
Jovanović
A
A
Department of Pharmacology, Medical Faculty, Belgrade, Yugoslavia.
Grbović
L
L
Zikić
I
I
Tulic
I
I
D000328:Adult; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D014599:Uterus / Q000098:blood supply*
D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin