Quinapril treatment restores the vasodilator action of insulin in fructose-hypertensive rats.
1. Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve insulin-resistance both experimentally and clinically. We therefore investigated the effects of quinapril, which has high tissue specificity for ACE, regarding the contribution of insulin to vascular contractions, as well as insulin sensitivity in a dietary rat model of insulin resistance. 2. Male Sprague-Dawley rats were divided into three groups: (i) rats fed normal chow (normal diet group); (ii) rats fed fructose-rich chow containing 40% fructose and 7% lard (fructose diet group); and (iii) rats fed fructose-rich chow plus quinapril (10 mg/kg per day; quinapril-treated group). 3. After 2 weeks, we evaluated systolic blood pressure, insulin sensitivity as assessed by steady state plasma glucose (SSPG) levels, response of aortic rings to phenylephrine (10-9 to 10-6 mol/L) in the presence or absence of insulin and the response of aortic rings to acetylcholine. 4. Feeding rats fructose-rich chow resulted in an elevation of blood pressure (P < 0.01) and SSPG levels (P < 0.01). Quinapril treatment significantly prevented increases in both blood pressure and SSPG, with a return to the levels seen in the normal diet group. 5. In the absence of insulin, the maximal contractile response to phenylephrine did not differ between the three groups. However, in the presence of insulin (100 mU/mL), the contractile response to phenylephrine (10-6 mol/L) was reduced by 22.8 +/- 1.2% in the normal diet group, although no insulin effects were observed in the fructose diet group (P < 0.01). Quinapril restored the inhibitory effect of insulin on phenylephrine-induced contractions. 6. In addition, the reduction in relaxation induced by acetylcholine in the fructose diet group was significantly reversed by quinapril treatment. 7. It is concluded that the fructose diet impairs the vasodilator effects of insulin as well as acetylcholine-induced relaxation in rat thoracic aortas. Quinapril prevented deterioration in the responses of the aortic rings, suggesting that ACE inhibitors may be useful for treating vascular insulin resistance.
Uchida
Takanori
T
Department of Internal Medicine II, Nagoya University School of Medicine, Nagoya, Japan.
Okumura
Kenji
K
Ito
Takayuki
T
Kamiya
Hiroki
H
Nishimoto
Yasuhiro
Y
Yamada
Michiharu
M
Tomida
Takahito
T
Matsui
Hideo
H
Hayakawa
Tetsuo
T
D000109:Acetylcholine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D005632:Fructose; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D000077583:Quinapril; D051381:Rats; D017207:Rats, Sprague-Dawley; D044005:Tetrahydroisoquinolines; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D007328:Insulin; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D005632:Fructose; D000109:Acetylcholine; D000077583:Quinapril