Time course alterations in vascular adrenergic responsiveness in the DOCA/NaCl-treated rat.

Abstract

Rats treated with desoxycorticosterone acetate and sodium chloride (DOCA/NaCl) developed a time-dependent increase in blood pressure which was associated with a reduced in vitro beta- and an elevated alpha-adrenergic responsiveness. Isoproterenol-induced relaxation of aortic smooth muscle from the DOCA-NaCl-treated rats was similar to controls 1 week after treatment, was significantly attenuated as the blood pressure began to rise (week 4) and was completely abolished when the blood pressure exceeded 150 mm Hg (week 12). The aortic smooth muscle sensitivity to norepinephrine was significantly increased prior to (week 1), during the rise (week 4) and during the maintenance of an elevated systolic blood pressure (greater than 150 mm Hg; week 12). No significant differences were observed between the two groups in either the contractile response of the aortic ring preparations to potassium chloride or in the relaxation properties in response to sodium nitrite. These results demonstrate that alterations in both the alpha- and beta-adrenergic responsiveness occur in the DOCA/NaCl-treated animal. The enhancement of the alpha-adrenergic responsiveness occurs prior to any change in blood pressure, while the attenuated beta-adrenergic responsiveness parallels the elevation in blood pressure, suggesting that these reciprocal alterations of adrenergic responsiveness may be responsible for the eventual development of hypertension induced with DOCA/NaCl treatment in rats.