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

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Abstract
Prolonged isoproterenol infusion (400 .mu.g/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.

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