The purpose of these studies was to evaluate structural and functional changes in a model of hypertension-induced cardiac hypertrophy in which vasodilator therapy prevented the increase in blood pressure. Uninephrectomized weanling (125 g) Sprague-Dawley rats received a Silastic implant containing deoxycorticosterone acetate (DOCA, 150 mg/kg) subcutaneously and were given drinking water containing sodium chloride and potassium chloride. Vasodilator antihypertensive treatment (hydralazine; HYD) was started immediately after DOCA implantation. The rise in blood pressure was prevented in DOCA + HYD (124±5.4 mm Hg, ±s.e.m) compared to DOCA (213±7.5 mm Hg), and blood pressure was not different from control (CON; 118±5.5 mm Hg). Hydralazine lowered blood pressure in CON + HYD (102+3.9 mm Hg) but this decrease was not significant (P>0.05). Hydralazine treatment prevented hypertension in DOCA + HYD but did not prevent development of cardiac hypertrophy (heart weight/body weight of DOCA + HYD 3.99±0.1 vs. DOCA 4.15±0.1; CON, 3.23±0.2 and CON+HYD 3.27±0.1). Coronary flow reserve measured by adenosine vasodilatation in a modified Langendorff isolated perfused rat heart model, was decreased in hearts from DOCA rats (41% increase in flow above baseline) compared to controls (CON, 132%; CON + HYD 139%), and was significantly improved in DOCA+HYD (98%). Morphometric evaluation of perfusion-fixed coronary arteries demonstrated a significant increase in the slope of the regression line comparing the square root of medial area vs. outer diameter in DOCA (0.619) compared to CON (0.501) and CON + HYD (0.491). Blood vessels from DOCA + HYD were not different from control (0.503). These studies suggest that significant alterations in coronary vascular structure and function occur in hypertension-induced cardiac hypertrophy. The coronary vasculature is responsive to blood pressure, independent of cardiac hypertrophy, although coronary deficits do remain after antihypertensive therapy. © 1988 Academic Press Limited.