Renal protective effects of angiotensin converting enzyme inhibitors.
Renal dysfunction and hypertension are closely associated. Hypertension causes approximately 25% of end-stage renal disease (ESRD) and develops in virtually every patient with advanced renal insufficiency from any cause. Although normalization of blood pressure can reduce mortality from uremia and ameliorate the progression of renal impairment in patients with established renal insufficiency from hypertension and diabetes, antihypertensive therapy alone is not totally effective in preventing progressive compromise of renal function--especially in blacks and diabetics, who are at high risk for developing ESRD. Of particular promise is the rapidly increasing understanding of the intrarenal autocrine and paracrine functions of angiotensin II produced locally by a tissue renin-angiotensin system. Consistent and convincing experimental data have demonstrated that angiotensin II plays many roles in the control of renal function and the kidney's response to injury. The intrarenal effects of angiotensin II include: 1) increase in the efferent arteriolar tone, resulting in increased glomerular capillary pressure, 2) promotion of mesangial cell contraction, 3) stimulation of proximal tubular Na+ reabsorption, and 4) possible growth hormone effects leading to hypertrophy or hyperplasia of vascular smooth muscle. Because of their favorable intrarenal hemodynamic effects (particularly reduction of glomerular capillary pressure), ACE inhibitors may provide a renal protective effect in addition to their systemic antihypertensive effects. Clinical trials evaluating the effect of ACE inhibition on the progression of renal insufficiency in hypertensives and diabetics are currently under way. Favorable results could lead to a significant decrease in the morbidity and mortality associated with hypertension.
Weder
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University of Michigan Medical Center, Department of Internal Medicine, Ann Arbor 48109-0356.
D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy; D007546:Isoquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects; D007676:Kidney Failure, Chronic / Q000209:etiology*; D007684:Kidney Tubules / Q000378:metabolism; D000077583:Quinapril; D012964:Sodium / Q000378:metabolism; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000804:Angiotensin II; D012964:Sodium; D000077583:Quinapril