Central cardiovascular effects of AVP and AVP analogs with V1, V2 and 'V3' agonistic or antagonistic properties in conscious dog.
To determine central cardiovascular effects of arginine vasopressin (AVP) in the dog, and the nature of the receptors involved, blood pressure (BP) and heart rate (HR) responses were monitored in 18 conscious dogs subjected to third ventricle (i.c.v.) infusions of either AVP or AVP analogs with agonistic or antagonistic properties towards V1, V2 and putative 'V3' receptors. Significant blood pressure (BP) increases were elicited by i.c.v. infusions of: (i) AVP at a rate of 0.01, 1 and 100 ng/min; (ii) the selective V1 agonist (F180, Ferring) at a rate of 1 and 100 ng/min, and (iii) the selective V1 antagonist, dEt2 Tyr(Me)DAVP at a rate of 100 ng and 400 ng/min. Pretreatment with another selective V1 antagonist (MeCAAVP) increased baseline BP and prevented AVP induced BP increase. Blood pressure was not altered by i.c.v. infusions of the selective V2 agonist dVDAVP, the selective V2 antagonist d(CH2)5[D-Ile2,Abu4]AVP, the putative 'V3' agonist vasopressin-(4-8) (Akzo Organon), mediating behavioral actions of AVP and by artificial CSF. Heart rate was significantly accelerated by AVP infused at a rate of 100 ng/min. The results reveal high sensitivity of the conscious dog to central pressor action of AVP and indicate that this effect is mediated by V1-like receptors. It is suggested that the pressor effect of the V1 antagonist may result from its partial agonistic properties towards central V1 receptors, however, it can not be excluded that endogenous AVP released under baseline conditions may exert tonic hypotensive effect mediated by a different population of V1 receptors, this effect being abolished by V1 antagonist. The results do not support involvement of V2 or 'V3' receptors in central cardiovascular actions of AVP.
Department of Clinical and Applied Physiology, Medical Academy of Warsaw, Poland.
B
B
Noszczyk
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Lon
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Szczepańska-Sadowska
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D017483:Receptors, Vasopressin / Q000187:drug effects*
D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin