title: Converting enzyme inhibition with captopril abolishes sympathoexcitation to euglycemic hyperinsulinemia in rats.
abstract: 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.
authors: Department of Biological Sciences, Lehman College, Bronx, New York 10468-1589, USA. martinmu@alpha.lehman.cunny.edu
authors: M S
authors: MS
authors: Muntzel
authors: J
authors: J
authors: Morales
authors: A
authors: A
authors: Akinsefunmi
mesh_terms: 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
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D000804:Angiotensin II; D002216:Captopril