THE IMPLICATION OF RENIN-ANGIOTENSIN SYSTEM ON RENAL INJURY SEEN IN DAHL SALT-SENSITIVE RATS

Angiotensin II (Ang II) progresses to remodeling of the cardiovascular system through nonhemodynamic as well as hemodynamic effects. There h ave been few data in vivo on whether subpressor concentration of Ang I I is exerted to injure directly the cardiovascular system in hypertens ion. To test this hypothesis, we investigated, using Dahl salt-sensiti ve (Dahl S) rats, whether subpressor dose of Ang II progresses to card iovascular injury observed in salt-induced hypertension. Recent studie s have provided evidence that renin-angiotensin inhibition protects ag ainst renovascular injury in human hypertension as well as in experime ntal animals. Particularly in the case of Dahl salt-sensitive rats, a genetic model of volume-dependent hypertension in humans, they are lik ely to develop more severe arterial and renal injuries than those seen in spontaneously hypertensive rats with similar blood pressure levels . The mechanism of the susceptibility to hypertensive injuries is unce rtain; however, renin-angiotensin inhibition significantly improved mo rphologic and functional injuries in the kidney of Dahl S rats. Conver sely, subpressor dose of Ang II infusion exacerbated renal function an d progressed to glomerulosclerotic lesions. Alterations of Ang II conc entration in physiologic range influenced morphologic and functional i njuries in Dahl S rats. Multivariate analysis revealed that activity o f the renin-angiotensin system is an independent risk factor to glomer ular injury in salt-induced hypertension. These data are in favor of t he therapeutic strategy in human hypertension that inhibition of renin -angiotensin system is of value to produce beneficial effects of blood pressure reduction on organ injuries. (C) 1997 American Journal of Hy yertension, Ltd.