Effects of quinapril and losartan on insulin sensitivity in genetic hypertensive rats with different metabolic abnormalities.
This study was designed to investigate the effects of the angiotensin-converting enzyme (ACE) inhibitor quinapril and the angiotensin II-receptor antagonist losartan on insulin sensitivity in two types of genetic hypertensive rats with insulin resistance. Quinapril (3 mg/kg) and losartan (10 mg/kg) decreased the systolic blood pressure to almost the same extent in both spontaneously hypertensive rats (SHRs) and Dahl salt-sensitive (Dahl S) rats. Quinapril increased the glucose requirement for the euglycemic clamp test in both SHRs and Dahl S rats, whereas losartan increased it in SHRs but not in Dahl S rats. The severity of the metabolic abnormalities may be responsible for the failure of losartan to improve the insulin sensitivity in Dahl S rats because serum insulin, total cholesterol, triglyceride, and free fatty acids (FFAs) were higher in the Dahl S rats than in SHRs. A kinin antagonist, Hoe 140, inhibited the increase in the glucose requirement by quinapril without affecting the depressor effect of quinapril in SHRs. In conclusion, quinapril improved the insulin sensitivity more effectively than did losartan in the genetic hypertensive rats with insulin resistance and relatively severe metabolic abnormalities. Based on our findings, one of the mechanisms underlying the difference between quinapril and losartan may thus be endogenous kinins.
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
H
H
Nakagawa
M
M
Daihara
H
H
Tamakawa
T
T
Nozue
K
K
Kawahara
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001774:Blood Chemical Analysis; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics*; D004357:Drug Synergism; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006973:Hypertension / Q000235:genetics*; D007328:Insulin / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D000077583:Quinapril; D051381:Rats; D011918:Rats, Inbred SHR; D044005:Tetrahydroisoquinolines
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007328:Insulin; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C065679:icatibant; D005947:Glucose; D019808:Losartan; D000077583:Quinapril; D001920:Bradykinin