Kinins contribute to the improvement of insulin sensitivity during treatment with angiotensin converting enzyme inhibitor.
Although angiotensin converting enzyme inhibitors and alpha 1-blockers have been reported to improve insulin sensitivity, their mechanisms of action have not been elucidated. To investigate the role of kinins in insulin sensitivity, we treated 4-week-old spontaneously hypertensive rats with either an angiotensin converting enzyme inhibitor (enalapril), an alpha 1-blocker (doxazosin), or an angiotensin II antagonist (losartan) for 3 weeks. A control group received no drugs. In addition, 18 rats treated with enalapril or doxazosin received a simultaneous administration of a kinin antagonist (Hoe 140). Glucose clamp testing was performed in each group. Enalapril (128 +/- 1 mmHg) and doxazosin (132 +/- 2 mmHg) decreased mean blood pressure compared with control levels (148 +/- 1 mmHg) (P < .01). The glucose requirement for the clamp test during the administration of enalapril (25.8 +/- 0.5 mg/kg per minute) or doxazosin (28.6 +/- 0.7 mg/kg per minute) was higher than that of the control group (19.8 +/- 0.5 mg/kg per minute) (P < .05). Although Hoe 140 did not alter the glucose requirement of doxazosin (27.8 +/- 0.5 mg/kg per minute), it decreased that of enalapril (22.6 +/- 0.9 mg/kg per minute) (P < .05) without affecting the changes in mean blood pressure induced by enalapril. In addition, losartan decreased mean blood pressure but did not affect the glucose requirement. Thus, the improvement in insulin sensitivity produced by an angiotensin converting enzyme inhibitor is mostly dependent on kinins but not on angiotensin II antagonism, and an alpha 1-blocker improves insulin sensitivity irrespective of kinins.
Tomiyama
H
H
Department of Cardiology, Surugadai Nihon University Hospital, Tokyo, Japan.
Kushiro
T
T
Abeta
H
H
Ishii
T
T
Takahashi
A
A
Furukawa
L
L
Asagami
T
T
Hino
T
T
Saito
F
F
Otsuka
Y
Y
D000704:Analysis of Variance; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D017292:Doxazosin / Q000494:pharmacology / Q000627:therapeutic use; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D015309:Glucose Clamp Technique; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007705:Kinins / Q000037:antagonists & inhibitors / Q000502:physiology*; D019808:Losartan; D008297:Male; D011188:Potassium / Q000097:blood; D051381:Rats; D011918:Rats, Inbred SHR; D012964:Sodium / Q000097:blood; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D001786:Blood Glucose; D007093:Imidazoles; D007328:Insulin; D007705:Kinins; D013777:Tetrazoles; D000804:Angiotensin II; D004656:Enalapril; C065679:icatibant; D012964:Sodium; D019808:Losartan; D017292:Doxazosin; D011188:Potassium; D001920:Bradykinin