Adrenergic regulation of adrenal and aortic heat shock protein

Surgical stress results in catecholamine secretion and selective induction of the major heat shock protein (HSP70) in the adrenal gland and in the vasculature. The adrenal response is cortical-specific and corticotropin-dependent. The vascular response occurs in the smooth muscle and is corticotropin-independent. We previously suggested that the vascular response was associated with adrenergic receptor stimulation. Herein, we report a series of experiments designed to test the hypothesis that aortic HSP70 messenger RNA (mRNA) induction occurs as a direct and specific response to alpha 1-adrenergic receptor stimulation.

Acute and chronic indwelling central venous catheter models were developed in the Wistar rat through which the following agents were infused: the alpha 1 agonist phenylephrine (0.14 mg/kg), the beta agonist isoproterenol (0.8 mg/kg), the alpha 1 antagonist prazosin (1 mg/kg), prazosin followed by phenylephrine, or saline solution alone. Hemodynamic responses were monitored; catecholamines were measured by high-performance liquid chromatography; 60 minutes after infusion, the animals were killed, and the adrenal glands and aortas were assayed for HSP70 mRNA expression on Northern blots.

Alpha 1 stimulation with phenylephrine resulted in marked hypertension, a reflexive bradycardia, and marked induction of aortic HSP70 mRNA. This effect could be completely abolished when the alpha 1 antagonist prazosin was administered before phenylephrine treatment. The beta agonist isoproterenol failed to induce aortic HSP70. A significant catecholamine response only occurred after prazosin administration.

These studies show a functional interaction between alpha 1 receptor stimulation and vascular HSP mRNA induction.