Coronary vascular function and morphology in hydralazine treated DOCA salt rats.
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 greater than 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.
Anderson
P G
PG
Department of Pathology, University of Alabama, Birmingham 35294.
Bishop
S P
SP
Digerness
S B
SB
D000818:Animals; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000502:physiology*; D003900:Desoxycorticosterone / Q000494:pharmacology*; D006830:Hydralazine / Q000494:pharmacology*; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains
D006830:Hydralazine; D003900:Desoxycorticosterone