PATHOPHYSIOLOGY OF ALTERED RENAL-FUNCTION IN RENAL VASCULAR HYPERTENSION

It is now clear that specific angiotensin-dependent mechanisms contrib ute importantly to the pathophysiology of hypertension (HT) and altere d renal function in models of two-kidney, one-clip (2-K, 1-C) HT in ra ts. The discovery of specific antagonists for angiotensin-converting e nzyme and the newer angiotensin receptor and kinin receptor antagonist s have allowed delineation of the contributions of these hormones to a ltered renal function in these models. The focus of interest in most o f these studies has been the nonclipped kidney, which would be expecte d to ameliorate elevated blood pressure by exhibiting a pressure diure sis and natriuresis in the environment of systemic HT. Antagonism of t he renin-angiotensin system in rat models of renal vascular HT indicat es that the effects of angiotensin attenuate renal hemodynamic and exc retory behavior, particularly in the nonclipped kidney. Furthermore, a ngiotensin attenuates the efficiency of autoregulation of renal hemody namics in the nonclipped kidney. Function of the clipped kidney appear s to be both angiotensin and perfusion pressure dependent. Evidence th at inhibition of angiotensin reverses or improves these altered hemody namic and excretory functions indicates that angiotensin may contribut e importantly to the pathophysiology of HT in these models by altering or impairing the ability of the nonclipped or ''normal'' kidney to ex crete sodium and volume. The precise roles of altered activity of vaso dilator hormones to contribute to these alterations of renal function remains to be defined. (C) 1994 by the National Kidney Foundation, Inc .