Abstract
Abstract
A study was performed to determine whether a constant 1-week exposure to either alpha or beta agonists in vivo would allow alteration or manipulation of the responses of rat aortic alpha- and beta-adrenergic receptors. Osmotic minipumps delivering either phenylephrine, isoproterenol, or propranolol for 7 days at a dose of 3.2, 4.2, or 5.2 mg/kg/day, respectively, were implanted in male Holtzman rats under halothane anesthesia. Seven days later, rats were killed and aortic ring preparations were used to measure alpha- and beta-adrenergic responses. In phenylephrine-pretreated rats, alpha-adrenergic responses, as measured by contractions induced by phenylephrine, were markedly reduced (P < 0.05) across a dose range of 10-9 to 10-6 M. In contrast, in these same phenylephrine-pretreated preparations, the beta-adrenergic responses involving isoproterenol-induced relaxation were significantly increased (P < 0.05) across a dose range of 10-7 to 10-5 M. Isoproterenol pretreatment for 7 days resulted in a statistically significant reduction of beta-adrenergic aortic relaxation, whereas the alpha-adrenergic responses to phenylephrine remained unchanged compared with controls. Propranolol pretreatment had no effect on either alpha- or beta-adrenergic responses. These findings indicate that the alpha agonist-induced response after in vivo pretreatment induces reciprocal changes in the functionally related beta-adrenergic apparatus, and also suggest linkage between these two receptors. In contrast, the beta response appears to desensitize or downregulate in response to beta agonist exposure in a manner that seems to be independent of or to operate in the absence of an alteration of the alpha response.
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