Converting enzyme inhibition with captopril abolishes sympathoexcitation to euglycemic hyperinsulinemia in rats.
Converting enzyme inhibition and angiotensin II receptor antagonism attenuate elevations in heart rate and plasma norepinephrine in response to insulin, suggesting that integrity of the renin-angiotensin system is necessary for insulin-induced sympathoexcitation. To test this, we infused vehicle (saline) in control experiments, or insulin (40 mU/min) during euglycemic clamp in captopril-pretreated (intravenously 2.5 mg/kg, then 1 mg/kg/h) and in nonpretreated urethane-anesthetized Wistar rats while measuring mean arterial pressure, heart rate, and lumbar sympathetic nerve activity. Although euglycemic hyperinsulinemia produced similar blood pressure (BP) increases in insulin-infused rats (change in mean arterial pressure: +9 +/- 3 mm Hg) compared with vehicle-controls (+6 +/- 2 mm Hg), insulin decreased blood pressure (BP) in captopril-pretreated insulin-infused rats (-8 +/- 3 mm Hg). Control rats developed mild heart rate increases (change in heart rate: +28 +/- 15 beats/min), contrasting with a marked tachycardia in insulin-infused rats (+82 +/- 13 beats/min) and a bradycardia in captopril-treated insulin-infused rats (-16 +/- 18 beats/min). As with heart rate, insulin-infused rats experienced large increases in lumbar sympathetic nerve activity (+ 127 +/- 29%), whereas small and equivalent elevations were observed in vehicle-treated rats (+39 +/- 24%) and in captopril-pretreated insulininfused rats (+61 +/- 13%). These observations demonstrate an attenuation of insulin-induced sympathetic activation by renin-angiotensin blockade with captopril in Wistar rats, and suggest that the renin-angiotensin system is critical for insulin to exert its sympathoexcitatory effects.
Muntzel
M S
MS
Department of Biological Sciences, Lehman College, Bronx, New York 10468-1589, USA. martinmu@alpha.lehman.cunny.edu
Morales
J
J
Akinsefunmi
A
A
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006946:Hyperinsulinism / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D000804:Angiotensin II; D002216:Captopril