Chronic angiotensin-converting enzyme inhibition and angiotensin II antagonism in rats with chronic renal failure.
The current study was undertaken to compare the organ protective effects of an angiotensin-converting enzyme inhibitor, temocapril, with those of an angiotensin II type 1 receptor antagonist, CS-866 (olmesartan medoxomil), alone or combined, in the remnant kidney model of rats. Eight-week-old spontaneously hypertensive male rats were subjected to five-sixths nephrectomy. At the age of 10 weeks, the rats were randomly allocated to groups that received two doses of CS-866 (CS-L, 3 mg/kg/day; CS-H, 10 mg/kg/day), temocapril (TEM, 10 mg/kg/day), CS-866 (3 mg/kg/day) plus temocapril (10 mg/kg/day), or a vehicle alone (untreated control group). Systolic blood pressure (SBP) and urinary protein excretion (UprotV) were measured every 2 weeks. When the rats were 18 weeks old, biochemical measurement and histologic examination were performed. All the drug treatments significantly reduced SBP, UprotV, glomerular sclerosis index (GSI), relative interstitial volume (RIV), and heart weight. The hypotensive effects were on the order of combination therapy > CS-H = TEM > CS-L. Correlational analysis was based on the values for SBP and UprotV derived from the average of values obtained when the rats were 12 to 18 weeks of age. UprotV, GSI, and RIV were found to be highly correlated with SBP among the individual rats pooled from all the groups, and the correlation was maintained among the group means. A similar correlation was found between heart weight and SBP. The results suggest that the organ protective effects of temocapril, CS-866, and combination therapy are closely related to the magnitude of their antihypertensive effects.
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004359:Drug Therapy, Combination; D007093:Imidazoles / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D000068557:Olmesartan Medoxomil; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism; D013777:Tetrazoles / Q000627:therapeutic use; D013841:Thiazepines / Q000494:pharmacology / Q000627:therapeutic use
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D013841:Thiazepines; D000068557:Olmesartan Medoxomil; C055603:temocapril hydrochloride; D007703:Peptidyl-Dipeptidase A