Role of bradykinin in insulin sensitivity and blood pressure regulation during hyperinsulinemia.
The purpose of these experiments was to determine in normotensive rats the role of endogenous bradykinin, prostaglandins, and nitric oxide in glucose metabolism and blood pressure response to hyperinsulinemia. Normotensive Wistar rats were treated with two different bradykinin antagonists, indomethacin or N omega-nitro-L-arginine methyl ester, concurrently with a euglycemic clamp with insulin infusion rates of 3 or 6 mU/kg per minute. Glucose uptake, steady-state plasma insulin levels, and insulin sensitivity index were determined over 2 hours. Bradykinin inhibition dramatically reduced glucose uptake and insulin sensitivity index during both the lower and higher insulin infusion rates to 30% and 32%, respectively, of values observed in control rats. Inhibition of prostaglandins or nitric oxide did not alter glucose metabolism in these rats. Blood pressure remained unchanged in the control group throughout the clamp but increased significantly in rats submitted to inhibition of bradykinin, prostaglandins, or nitric oxide, suggesting that these vasodilator systems tend to counteract the hypertensive effect of hyperinsulinemia. The counterregulatory component attributable to bradykinin was about twice as great as that attributable to nitric oxide. These findings suggest that insulin infusion in normotensive Wistar rats fails to raise blood pressure because its effects are offset by mobilization of vasodilator mechanisms, such as bradykinin, prostaglandins, and nitric oxide. Bradykinin seems to play the most important homeostatic role under these conditions, because its inhibition significantly reduces insulin sensitivity and allows blood pressure to rise.
Kohlman
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O
Division of Nephrology, Escola Paulista de Medicina Sao Paulo, Brazil.
Neves
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Fde A
Ginoza
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Tavares
A
A
Cezaretti
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Zanella
M T
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Ribeiro
A B
AB
Gavras
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I
Gavras
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D001120:Arginine; D005947:Glucose; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin