Pressor responses in rats following intravenous dynorphin A(1-13) administration are blocked by AVP-V1 receptor antagonism.
Hemodynamic (blood pressure and heart rate) experiments were conducted in conscious and/or anesthetized male Sprague-Dawley (S.D.), heterozygous and homozygous Brattleboro rats given intravenous (iv) dynorphin A(1-13), arginine vasopressin (AVP), norepinephrine (HCl, (NE) or sterile saline before and 10 min after an iv bolus injection of a specific receptor antagonist. These receptor blockers (kappa receptor antagonist Mr2266, alpha adrenoceptor antagonist phentolamine HCl or the AVP-V1 receptor antagonist d(CH2)5Tyr-(Me)AVP were given in equimolar concentrations (15 nmol/kg iv). In all conscious S.D. groups, iv injection of AVP (60 pmol/kg), NE (12.5 nmol/kg) and dynorphin A(1-13) (60 nmol/kg) evoked significant increases in mean arterial pressure (MAP) associated with concomitant bradycardia. The hemodynamic responses to 'both' AVP and dynorphin A(1-13) were blocked if given subsequent to AVP-V1 administration but not following phentolamine or Mr2266 pretreatment. The pressor and bradycardic responses of conscious heterozygous and homozygous Brattleboro rats after iv AVP or dynorphin again were only blocked by the AVP-V1 receptor antagonist. Anesthetized heterozygous and homozygous Brattleboro rats again showed pressor responses following iv AVP, NE or dynorphin A(1-13) but with slight or no associated bradycardia. The rise in blood pressure with AVP 'and' dynorphin A(1-13) in these groups also was only blocked by the d(CH2)5Tyr(Me)AVP antagonist. The results indicate that the pressor responses of rats given intravenous dynorphin A(1-13) involve the interaction of AVP-V1 receptors and suggest a functional interaction of these two neuropeptides in the modulation of vascular tone.
Thornhill
J
J
Department of Physiology, University of Saskatchewan, Saskatoon, Canada.
Gregor
L
L
Pittman
Q
Q
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004399:Dynorphins / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010902:Pituitary Gland / Q000737:chemistry; D051381:Rats; D011919:Rats, Inbred Strains; D017483:Receptors, Vasopressin
D057911:Angiotensin Receptor Antagonists; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D004399:Dynorphins; D009638:Norepinephrine