Comparative hypertensionology-renal dopaminergic activity in experimental hypertensive rats

Abstract

In our laboratory, it had been found that the renal natriuretic and depressor systems are suppressed in essential hypertension, and that suppression of the dopaminergic system may be primary and dominant in this condition. Moreover, close relationships among the renal dopamine, kallikrein-kinin, and prostaglandin systems have also been found. Therefore, we attempted to evaluate the pathogenetic and pathophysiological role of renal dopamine in connection with renal kallikrein-kinin and prostaglandin systems in various experimental hypertensive models. Two kidney 1 clip hypertensive rats (2K1C), 5/6 reduced renal mass hypertensive rats (5/6 RRM), deoxycorticosterone acetate-salt hypertensive rats (DOCA-salt), spontaneously hypertensive rats/Izumo (SHR/Iz), Dahl salt sensitive hypertensive rats/John Rapp (Dahl/Jr), Dahl/Iwai (Dahl/Iw), and respective controls were employed in this study. Urinary excretions of free dopamine (uDA), kallikrein (uKAL), and prostaglandin E2 (uPGE2) were measured before, during and after treatment in each of these hypertensive models. In these experimental hypertensive models, renal dopamine in DOCA-salt and SHR/Iz, and renal kallikrein in 2K1C, 5/6 RRM and two types of Dahl strains were primarily and dominantly suppressed in the renal natriuretic and depressor systems. Renal dopamine was transiently suppressed in Dahl/Jr, and PGE2 was suppressed in the two types of Dahl strains. Compensatory augmentation of renal kallikrein was found in DOCA-salt and SHR/Iz, and that of PGE2 was found in 5/6 RRM and DOCA-salt. Although these three renal natriuretic depressor systems are suppressed in Dahl/Jr, the dominantly suppressed system is not renal dopamine but renal kallikrein. Thus, it was summarized that, 1) decreased renal dopamine production is important in the pathogenesis of human essential hypertension, 2) pressor mechanisms of experimental hypertensive rats are different from human essential hypertension, 3) decreased renal dopamine is important in DOCA-salt and SHR/Iz, 4) decreased renal kallikrein is the dominant mechanism in the pathogenesis of 2K1C, 5/6 RRM, Dahl/Jr and Dahl/Iw hypertensive rats, and 5) we have to be careful when considering human essential hypertension through results taken from experimental rat hypertensive models.