Among vascular beds, that of the kidney is especially responsive to
angiotensin II, perhaps a reflection of the fact that the
renin-
angiotensin axis is normally a volume-control rather than a pressure-control system. The dose of
angiotensin required to induce renal vasoconstriction in a normal subject receiving a typical, liberal
sodium intake, for example, is about an order of magnitude lower than that required to induce a pressor response. Indeed, compelling arguments can be made for a local, intrarenal role as
angiotensin's first action in phylogeny, with additional cardiovascular and endocrine responses arising later. In patients with
essential hypertension, in whom renal vascular tone is commonly increased, converting
enzyme inhibitors such as
teprotide and
captopril induce a potentiated acute renal vascular response: renal blood flow increases more than it does in normal subjects. The result is a consistent, early increase in
sodium excretion and an occasional increase in glomerular filtration rate. Reduced
aldosterone release consequent to the block of
angiotensin II formation also contributes to the natriuresis and results in positive
potassium balance. With long-term
therapy, renal function tends to be very well maintained. In
renal artery stenosis the situation is more complex: as perfusion pressure distal to the
stenosis falls, typically afferent arteriolar dilatation exists and glomerular capillary pressure tends to be maintained by an increase in postglomerular resistance. To the extent that this increase is
angiotensin-mediated, suppression of
angiotensin formation with
captopril can reduce glomerular capillary pressure and thus filtration rate. This is well tolerated in the patient with unilateral
stenosis and a healthy contralateral kidney, but can provoke
renal failure when the
stenosis is bilateral or involves a
solitary kidney. The available evidence suggests that the converting
enzyme inhibitor's influence on the kidney primarily reflects reduced
angiotensin II formation, although reduced
kinin degradation or increased
prostaglandin synthesis may also have an influence. Whatever the mechanism responsible for the renal response, there are compelling reasons for suspecting that the salutary action of
captopril on the kidney makes a substantial contribution to its over-all efficacy in the treatment of
hypertension.