The pathophysiological role of renal dopamine and kallikrein in deoxycorticosterone acetate (DOCA)-salt treated rats.

Abstract

To elucidate the pathophysiological role of the renal dopamine (DA) and kallikrein-kinin systems in volume dependent hypertension under excess mineralocorticoid, the urinary excretions of DA and kallikrein (KAL) were investigated in DOCA-salt treated rats (5 week-old Sprague-Dawley rats, DOCA 100mg pellet, s.c., 1% saline ingestion for 4 weeks, n = 7) for comparison with those of control rats (vehicle, 1% saline ingestion for 4 weeks, n = 10). In vehicle, systolic blood pressure (SBP), urinary excretion of free DA (UDA) and kallikrein (UKAL) did not change through the study. In DOCA treated rats, marked natriuresis was observed with sodium load. SBP and UKAL significantly increased at the 4th week and at the 2nd week, respectively. UDA increased significantly to the peak level at the 1st week, and then decreased gradually. At the 4th week, UDA was significantly lower in DOCA-treated rats than that of vehicle rats. A significant inverse correlation was found between UDA and SBP, and UKAL correlated positively with SBP and urinary excretion of sodium and negatively with UDA in DOCA treated rats. These results suggest that the augmentation of renal dopaminergic activity which may in part cause sodium escape appears at the early stage of DOCA-salt treatment, but this augmentation is subsequently blunted; volume and sodium retention may be associated with the blood pressure elevation at the late stage of DOCA-salt treatment, and that the augmentation of renal kallikrein-kinin system may be a compensatory response to sodium and volume retention in DOCA-salt treated rats.