Effects of troglitazone and temocapril in spontaneously hypertensive rats with chronic renal failure.
OBJECTIVE
The insulin resistance state is common in humans and animals with chronic renal failure. We investigated the effects of troglitazone, an insulin sensitizer, on blood pressure and nephropathy in the remnant kidney model of spontaneously hypertensive rats (SHR).


METHODS
Eight-week-old male SHR were subjected to five-sixth nephrectomy. At the age of 10 weeks, the rats were randomly allocated to groups that received troglitazone (70 mg/kg per day); the angiotensin converting enzyme inhibitor temocapril (10 mg/kg per day); troglitazone (70 mg/kg per day) plus temocapril (10 mg/kg per day), or a vehicle alone as an untreated control group. Systolic blood pressure (SBP) and urinary protein excretion were measured every 2 weeks. At the age of 22 weeks, biochemical measurements and histological examination were performed.


RESULTS
Blood glucose, glycosylated hemoglobin and body weight were similar in the four groups. SBP, serum creatinine and glomerular sclerosis index were significantly reduced in all treated groups compared with those in the control group. Urinary protein excretion, glomerular volume and aortic media thickness were significantly decreased in temocapril-treated rats and troglitazone plus temocapril-treated rats compared with those in control rats. Although antihypertensive effects of troglitazone were minute compared with those of temocapril or troglitazone plus temocapril, there was no significant difference between the glomerular sclerosis indices in these three drug-treated groups.


CONCLUSIONS
The results suggest that troglitazone has renoprotective effects in this rat model. These effects might be due to the inhibition of growth factors rather than to the minute hypotensive effect, although the mechanism remains to be elucidated.
Yoshida
K
K
Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Sendai, Japan. kazunori@mail.cc.tohoku.ac.jp
Kohzuki
M
M
Xu
H L
HL
Wu
X M
XM
Kamimoto
M
M
Sato
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011507:Proteinuria / Q000150:complications / Q000188:drug therapy; D051381:Rats; D011918:Rats, Inbred SHR; D013841:Thiazepines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D000806:Angiotensin-Converting Enzyme Inhibitors; D002839:Chromans; D007004:Hypoglycemic Agents; D013841:Thiazepines; D013844:Thiazoles; D045162:Thiazolidinediones; C055603:temocapril hydrochloride; D000077288:Troglitazone