Converting enzyme inhibition with captopril abolishes sympathoexcitation to euglycemic hyperinsulinemia in rats

• Published in: American journal of hypertension 2001-06, Vol.14 (6), p.592-598
• Main Authors: Muntzel, Martin S, Morales, Jose, Akinsefunmi, Adesola
• Format: Article
• Language: English
• Subjects: angiotensin II; Angiotensin II - antagonists & inhibitors; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; blood pressure; Blood Pressure - drug effects; Captopril - administration & dosage; Captopril - pharmacology; Cardiology. Vascular system; Experimental diseases; heart rate; Heart Rate - drug effects; Hyperinsulinism - physiopathology; Hypoglycemic Agents - pharmacology; Insulin; Insulin - pharmacology; lumbar; Male; Medical sciences; Rats; Rats, Wistar; Renin-Angiotensin System - drug effects; sympathetic nerve activity; Sympathetic Nervous System - drug effects
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/S0895-7061(00)01319-4

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 insulin-infused 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.