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CARDIOVASCULAR ANESTHESIA

Resensitization of Blood Pressure Response to µ-Opioid Peptide Agonists After Acute Desensitization

Department of Pharmacology, Weill Medical College of Cornell University, New York, New York

Address correspondence and reprint requests to Hazel H. Szeto, MD, PhD, Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Ave., New York, NY 10021. Address e-mail to hhszeto{at}mail.med.cornell.edu

IV administration of µ-opioid peptide agonists (DAMGO, DALDA, and [Dmt¹]DALDA) results in a transient, naloxone-sensitive, increase in blood pressure in awake sheep. Despite significant differences in pharmacokinetics, these blood pressure responses all last <15 min. The lack of correlation between half-life and duration of action suggested rapid desensitization. When a second dose of the same agonist was repeated 30 min later, the response was completely abolished. An increase in blood pressure and rapid desensitization was also observed with the -opioid agonist (U50488H), whereas -agonists (DPDPE and DELT) had no effect on blood pressure. The response to DAMGO was abolished after prior exposure to DAMGO or DALDA, but there was no evidence of cross-desensitization between µ and , or µ and , opioid agonists. Full resensitization of the blood pressure response occurred by 4 h for DAMGO (t_1/2 = 15 min) and by 48 h for [Dmt¹]DALDA (t_1/2 = 1.8 h). These data support our hypothesis that the transient nature of the blood pressure response to µ-opioid agonists is caused by rapid desensitization and suggest that the rate of resensitization is dependent on the pharmacokinetics of the agonist.

IMPLICATIONS: This report suggests that rapid desensitization accounts for the transient increase in blood pressure observed after IV administration of µ-opioid agonists, and that the rate of resensitization is a function of the elimination half-life of the agonist.

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