Renal protective effects of blocking the intrarenal renin-angiotensin system: angiotensin II type I receptor antagonist compared with angiotensin-converting enzyme inhibitor.
The present study compared renoprotective effects of angiotensin II type I receptor antagonist (AT1RA) with angiotensin converting enzyme inhibitor (ACEI), and their influence on the renin-angiotensin-system (RAS). Experimental nephrotic syndrome was induced in SD rats by repeated peritoneal injections of puromycin. Twenty-eight rats were randomly divided into four groups: normal control, nephrotic control, ACEI-treated, and AT1RA-treated groups. Serum, urine, and renal tissue were collected for study at the end of 12 weeks. Compared with those of the nephrotic control group, urinary protein was less and renal function was better in both treated groups. The glomerular and interstitial damage indexes of both ACEI- and AT1RA-treated rats were lower than those of nephrotic control rats, with no significant difference observed between the two treated groups. Local renal ACE activity and angiotensin II concentration were elevated in nephrotic rats (p< 0.01). However, there is no significant difference in circulating RAS, renal tissue renin, and aldosterone between the normal control and nephrotic control rats. As expected, enalapril inhibited the local renal ACE activity and significantly decreased angiotensin II (p< 0.01). Intrarenal ACE activity and angiotensin concentration returned to normal levels after treatment with irbesartan (p< 0.01). In conclusion, AT1RA and ACEI have comparable renal protective effects, and these protective effects were associated with the inhibition of intrarenal ANG II.
Institute of Nephrology, Beijing Medical University, PR China.
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Zhou
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Yu
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Li
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Zhang
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Wang
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D005355:Fibrosis / Q000503:physiopathology / Q000652:urine; D000077405:Irbesartan; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D008297:Male; D009404:Nephrotic Syndrome / Q000473:pathology / Q000503:physiopathology / Q000652:urine; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012084:Renin-Angiotensin System / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D004656:Enalapril; D000077405:Irbesartan