Changes in renal vascular reactivity at various stages of deoxycorticosterone hypertension in rats.

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Abstract
The possible contribution of increased vascular reactivity to the development of deoxycorticosterone acetate (DOCA) hypertension was studied in rats. Changes in vascular reactivity were studied in isolated, constant-flow perfused kidneys of male Sprague-Dawley rats post unilateral nephrectomy which received a single s.c. implant of Silastic containing 100 mg/kg of DOCA and were given 0.9% NaCl plus 0.2% KCl solution to drink. Age- and sex-matched control rats (CR) received Silastic implants. The hypertensive rats were studied at 4 days (prehypertensive stage) and 61 days (chronic hypertensive stage) after implantation. At an average of 4 days, blood pressure in DOCA-treated rats did not differ significantly from that measured prior to implantation, and renal vascular resistance was similar to that in the matched controls. Renal vascular reactivity to norepinephrine (NE), vasopressin (ADH) and angiotensin II (A II) was enhanced in the DOCA-treated rats. Dose-response curves for kidneys of the prehypertensive rats showed a parallel leftward shift, reduced ED50 and decreased threshold dose. After an average period of 61 days, blood pressure in the DOCA-treated rats was 189.2 .+-. 3.5 mm Hg, and renal vascular resistance at maximal vasodilation was significantly greater (P < 0.0001) than in CR. Renovascular reactivity to NE, ADH and A II was markedly enhanced. Dose-response curves were characterized by a leftward shift, steeper slopes, increased maximal responses, decreased ED50 and threshold doses. Enhanced vascular reactivity clearly precedes and may initiate the rise in arterial pressure in DOCA-treated rats. The initial increase in response to vasoconstrictor substances is attributed to an enhanced sensitivity of vascular smooth muscle, but in the chronic stage of hypertension, structural changes in the resistance vessels, secondary to the rise in arterial pressure, are the main mechanisms responsible for the intensified reactivity.