Angiotensin II receptor blockade limits glomerular injury in rats with reduced renal mass.

Abstract

The effects of angiotensin II (All) blockade were compared with the effects of angiotensin converting enzyme inhibition in rats with reduced nephron number. Rats were subjected to fivesixths renal ablation and divided into four groups with similar values for blood pressure and serum creatinine after 2 wk. Group 1 then served as untreated controls, while group 2 received the All receptor antagonist MK954 (which has previously been designated DuP753), group 3 received the converting enzyme inhibitor enalapril, and group 4 received a combination of reserpine, hydralazine, and hydrochlorothiazide. Micropuncture and morphologic studies were performed 10 wk later. Converting enzyme inhibition, All receptor blockade, and the combination regimen were equally effective in reversing systemic hypertension (time-averaged systolic blood pressure: group 1, 185±5 mmHg; group 2, 125±2 mmHg; group 3, 127±2 mmHg; group 4, 117±4 mmHg). Micropuncture studies showed that glomerular transcapillary pressure was reduced significantly by converting enzyme inhibition and by AII blockade but not by the combination regimen (5P: group 1, 49±1 mmHg; group 2, 42±1 mmHg; group 3, 40±2 mmHg, group 4, 47±1 mmHg). Reduction of systemic blood pressure was associated with the development of markedly less proteinuria and segmental glomerular sclerosis in rats receiving enalapril and MK954 but not in rats receiving the combination regimen (prevalence of glomerular sclerotic lesions: group 1, 41±4%; group 2, 9±1%; group 3,9±1%; group 4, 33±6%). These results indicate that the effects of converting enzyme inhibition on remnant glomerular function and structure depend on reduction in All activity and are not attributable simply to normalization of systemic blood pressure. (J. Clin. Invest. 1992. 766-771.)

Angiotensin AT1 receptor antagonism and protection against cardiovascular end-organ damage

“…Lafayette 27 has reported that losartan reduced BP, glomerular transcapillary pressure and inhibited the development of proteinuria and segmental glomerular sclerosis in 5/6 nephrectomised rats. Interestingly, he also reported that a combined treatment of reserpine, hydralazine and hydrochlorothiazide had no effect on these parameters, although the combination reduced BP.…”

ACE-I vs angiotensin II receptor antagonists: prevention of renal injury in chronic rat models

“…27 Subsequent studies in the same model have confirmed these findings using different agents. [28][29][30][31][32][33] In addition, Kakinuma et al 28 found similar degrees of protection from arterial wall thickening with ACE-I and AT 1 RA.…”

“…The first study in this well-established model of secondary focal and segmental glomerulosclerosis by Lafayette et al 27 compared the effects of the ACE-I enalapril, the AT 1 RA losartan, and combination antihypertensive therapy with hydralazine, reserpine, and hydrochlorothiazide, commencing 2 weeks after surgery. After 19 weeks of therapy and equivalent blood pressure control in all treatment groups, animals in both the ACE-I and AT 1 RA groups had significantly less proteinuria than did untreated controls and combination antihypertensive-treated rats.…”

Renal Protective Effects of Blocking the Intrarenal Renin-Angiotensin System: Angiotensin II Type I Receptor Antagonist Compared with Angiotensin-Converting Enzyme Inhibitor.

“…After treatment with irbesartan, local renal ACE activity and angiotensin II concentration returned to normal levels (p < 0.01 vs. the nephrotic control group). There was no Angootensin-converting enzyme inhibitor has been successfully used to ameliorate proteinuria and retard the progression of glomerular sclerosis (20). The superiority of ACEI to other antihypertensive drugs at curbing the progression of renal fibrosis demonstrated the importance of the RAS in the progression of renal disease.…”