New antagonists of the vasopressin receptor mediated contraction in rat tail artery.
A perfused isolated rat tail artery preparation was employed to study antagonistic properties of four newly synthesized arginine-vasopressin (AVP) analogues against the V1 receptor. The activity of the agents SCATyr(Me)AVP, OCATyr(Me)AVP, OCAAVP and SCAAVP was related to that of a recognized antagonist d(CH2)5Tyr(Me)AVP. SCATyr(Me)AVP elicited outstanding antagonistic properties by blocking at concentration of 10(-7) M nearly completely the constrictory activity of AVP. At concentration of 10(-9) M the agent inhibited the AVP-induced constriction of artery about 40 times more effectively than the oxytocin (OXT)-induced constriction. The results obtained prove the validity of the structure-activity relationship based search for new potent V1 receptor antagonists.
Petrusewicz
J
J
Department of Biopharmaceutics and Pharmacodynamics, University of Gdansk, Poland.
Damasiewicz
B
B
Kaliszan
R
R
Juzwa
W
W
Lammek
B
B
Derdowska
I
I
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects*; D017483:Receptors, Vasopressin; D013329:Structure-Activity Relationship; D013623:Tail; D014661:Vasoconstriction / Q000187:drug effects*; D014667:Vasopressins / Q000378:metabolism*
D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D014667:Vasopressins; D001127:Arginine Vasopressin