ADRENERGIC REGULATION OF ADRENAL AND AORTIC HEAT-SHOCK PROTEIN

Background. Surgical stress results in catecholamine secretion and sel ective induction of the major heat shock protein (HSP70) in the adrena l gland and in the vasculature. The adrenal response is cortical-speci fic and corticotropin-dependent. The vascular response occurs in the s mooth muscle and is corticotropin-independent. We previously suggested that the vascular response teas associated with adrenergic receptor s timulation. Herein, we report a series of experiments designed to test the hypothesis that aortic HSP70 messenger RNA (mRNA) induction occur s as a direct and specific response to alpha(1)-adrenergic receptor st imulation. Methods. Acute and chronic indwelling central venous cathet er 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 p razosin (1 mg/kg), prazosin followed by phenylephrine, or saline solut ion alone. Hemodynamic responses were monitored; catecholamines were m easured by high-performance liquid chromotography; 60 minutes after in fusion, the animals were killed, and the adrenal glands and aortas wer e assayed for HSP70 mRNA expression on Northern blots. Results. Alpha( 1) stimulation with phenylephrine resulted in marked hypertension, a r eflexive bradycardia, and marked induction of aortic HSP70 mRNA. This effect could be completely abolished when the alpha(1) antagonist praz osin was administered before phenylephrine treatment. The beta agonist isoproterenol failed to induce aortic HSP70. A significant catecholam ine response only occurred after prazosin administration. Conclusions. These studies show a functional interaction between alpha(1) receptor stimulation, and vascular HSP mRNA induction.