Cardiovascular and renal protective effects of losartan in spontaneously hypertensive rats with diabetes mellitus.
1. Cardiovascular and renal benefits of a specific angiotensin II (AII) receptor antagonist, losartan (LOS), were assessed in diabetic rats with renal impairment. 2. Uninephrectomized SHR made diabetic by streptozotocin administration were given LOS (5 mg/kg per day, i.p.) alone, captopril (CAP) (50 mg/kg per day, i.p.) alone, or a combination of CAP and LOS via osmotic minipumps for 8 weeks. 3. Both CAP alone and LOS alone completely blocked the development of hypertension in diabetic SHR in the same manner. CAP + LOS did not enhance the antihypertensive effects of LOS alone or CAP alone. 4. CAP + LOS, LOS alone and CAP alone significantly decreased urinary protein excretion and serum creatinine to the same extent. 5. These results indicate that both LOS and CAP exert antihypertensive and renoprotective effects in this model: these actions are mainly through inhibition of AII production.
Kohzuki
M
M
Section of Internal Medicine and Disability Prevention, Tohoku University Graduate School, Sendai, Japan.
Yasujima
M
M
Liu
P F
PF
Obara
K
K
Kanazawa
M
M
Yoshida
K
K
Saito
T
T
Sato
T
T
Abe
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000517:prevention & control*; D019808:Losartan; D008297:Male; D009392:Nephrectomy; D051381:Rats; D011918:Rats, Inbred SHR; D013777:Tetrazoles / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D002216:Captopril; D019808:Losartan