Enhanced cardiovascular reactivity to desmopressin in water-restricted rats: facilitatory role of immunosuppression.
There is considerable evidence suggesting that vasopressin may play an important role in regulating cardiovascular homeostasis. In the present study the effects of immunosuppressant drugs, ciclosporin and tacrolimus on arterial blood pressure (BP) and heart rate (HR) responses to desmopressin (DDAVP) were compared in anesthetized normally hydrated and 24-h water-restricted rats. When injected intravenously, single bolus doses of DDAVP (0.5-8.0 micrograms/kg) elicited dose-dependent decreases in BP and also attenuated the HR. The enhancement of the vasodepressor response to DDAVP (4 micrograms/kg) was produced 15 min after the intravenous injection of either ciclosporin (3 mg/kg) or tacrolimus (25 micrograms/kg) accompanied by reduction in HR in water-restricted animals, but the response in euhydrated animals remained less modified after the bolus injections of immunosuppressants and DDAVP. To elucidate the possible contribution of the renal vascular system in water-restricted rats, ciclosporin was administered intravenously, followed 15 min later by 4 micrograms/kg injections of arginine vasopressin (AVP) or DDAVP into the renal artery, but there was no significant change in both the cardiovascular parameters as compared with the responses obtained with agonists alone. The present results indicate that the augmentation of the cardiovascular response to DDAVP by ciclosporin and tacrolimus in water-restricted anesthetized rats appears to be mediated by the release of endogenous vasodilatory mediators.
Tyagi
M G
MG
Department of Pharmacology & Clinical Pharmacology, Christian Medical College, Bagayam, Vellore, India. Abraham@cmc.emet.in
Thomas
M
M
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology; D013997:Time Factors; D014868:Water Deprivation / Q000502:physiology*
D007166:Immunosuppressive Agents; D001127:Arginine Vasopressin; D016572:Cyclosporine; D003894:Deamino Arginine Vasopressin; D016559:Tacrolimus