Selective Down Regulation of Vascular β1 Adrenergic Receptors After Prolonged Isoproterenol Infusion

Abstract

Prolonged isoproterenol infusion (400 micrograms/kg/h for 4 days) in rats was previously shown to produce a reduction in the sensitivity of both cardiac and vascular beta-adrenergic receptors without affecting responsiveness to alpha 1 agonists or phosphodiesterase inhibitors in either vascular or cardiac muscle. The present study was designed to determine if the loss in beta receptor responsiveness was similar for both beta 1 and beta 2 vascular receptors. The rat jugular vein was previously shown to relax in response to both norepinephrine and isoproterenol with norepinephrine-induced relaxation being mediated by interaction with beta 1 adrenergic receptors and isoproterenol-induced relaxation being mediated by its interaction with beta 2 vascular receptors. Using this preparation, tissues from isoproterenol-infused rats were approximately threefold less responsive to isoproterenol when compared to responses in tissues from saline-treated rats. Relaxation to norepinephrine in jugular veins from isoproterenol-infused rats was virtually abolished relative to the response in saline-treated animals. These data suggest that beta 1-adrenergic receptors in blood vessels are considerably more susceptible to down regulation than are beta 2-adrenergic receptors. This observation may have importance in both the therapy of congestive heart failure, where down regulation of beta-adrenergic receptors has been observed, and in our understanding of the mechanism for the inotropic effects of beta receptor agonists.