The effect of angiotensin-converting enzyme (ACE) inhibitors on renal function in the hypertensive patient is related both to the glomerular actions of angiotensin II and to the mechanism of autoregulation of the glomerular filtration rate (GFR) . Angiotensin II constricts both the afferent and efferent arterioles, but preferentially increases efferent resistance . At least three factors may contribute to this response:
- The efferent arteriole has a smaller diameter in the basal state; as a result, further constriction at this site will produce a greater increase in resistance than at the afferent arteriole .
- Angiotensin II stimulates the release of the vasodilator nitric oxide from the afferent arteriole, thereby minimizing constriction at this site .
- Angiotensin II minimizes vasoconstriction at the afferent arteriole via the stimulation of angiotensin II type 2 receptors, which results in vasodilation through a cytochrome P-450 dependent pathway .
The net effect of the more prominent increase in efferent tone is that the intraglomerular pressure is stable or increased, thereby tending to maintain or even raise the GFR. In addition to these arteriolar actions, angiotensin II constricts the mesangial cells, an effect that tends to lower the GFR by decreasing the surface area available for filtration.
An overview of the renal effects of ACE inhibitors will be reviewed here. The use of ACE inhibitors and angiotensin receptor blockers in patients with kidney disease are presented in detail elsewhere. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults" and "Treatment of hypertension in patients with diabetes mellitus".)
ANGIOTENSIN II AND AUTOREGULATION OF GFR
As the renal perfusion pressure is diminished (due for example to antihypertensive therapy), the kidney is initially able to maintain both blood flow and glomerular filtration via the phenomenon of autoregulation (figure 1) . The first part of the autoregulatory response is decreased afferent (precapillary) arteriolar tone, thereby allowing more of the systemic pressure to be transmitted to the glomerulus. Afferent dilatation is mediated both by tubuloglomerular feedback and by a direct myogenic response. With more marked reductions in renal perfusion pressure, renin release is stimulated; the ensuing increase in angiotensin II production maintains both intraglomerular pressure and the GFR via a preferential increase in resistance at the efferent arteriole . The net effect is that the GFR and renal blood flow do not begin to fall until these autoregulatory changes in arteriolar resistance are maximized.