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(Hypertension. 1998;31:104.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Acute Effects of Blood Pressure Elevation on Insulin Clearance in Normotensive Healthy Subjects

Christopher J. O’Callaghan; Karla Komersova; William J. Louis

From the Clinical Pharmacology and Therapeutics Unit, University of Melbourne, Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, Australia.

Abstract—Reduced clearance of insulin from plasma contributes to the hyperinsulinemia associated with essential hypertension (EH); however, the association between impaired insulin clearance and EH remains unexplained. Whether elevated blood pressure (BP) affects insulin clearance is unknown; therefore, we used the hyperinsulinemic euglycemic clamp to determine the effects of BP elevation on insulin clearance and sensitivity in eight healthy volunteers. Placebo infusion increased mean BP by 2.6±1.6 mm Hg, which was significantly less than rises produced by phenylephrine, an ₁-adrenoceptor agonist (+11±1.8 mm Hg, P<.05), or by angiotensin II (+13±1.3 mm Hg, P<.01). Although ß-adrenoceptor stimulation with isoproterenol did not change mean BP (+3.6 mm Hg, P=NS), it significantly increased systolic pressure (+23±2.8 mm Hg versus +2.3±4.6 mm Hg with placebo P<.01). Insulin secretion (ie, C-peptide concentrations) was not affected by any of the treatments; however, phenylephrine significantly reduced the metabolic clearance rate of insulin (MCR_insulin) (16.6±1.0 mL/kg per minute with placebo versus 13.6±0.7 mL/kg per minute with phenylephrine, P<.01) and thereby increased plasma insulin concentrations (66±5.1 µU/mL with placebo versus 79±4.1 µU/mL with phenylephrine, P<.05). Phenylephrine also increased glucose utilization (42±5.8 µmol/kg per minute during placebo versus 58±4.8 µmol/kg per minute during phenylephrine, P<.05); however, this was proportional to the increased insulin concentrations; therefore, insulin sensitivity was unchanged. MCR_insulin and plasma insulin concentrations were not affected by angiotensin II; however, glucose utilization increased to 51±2.7 µmol/kg per minute (P<.01 versus placebo), indicating insulin sensitivity was increased. MCR_insulin was unaffected by isoproterenol. Thus, -adrenergic stimulation but not increased BP per se is a potent regulator of insulin clearance and plasma insulin concentrations.

Key Words: insulin • hypertension, essential • sympathetic nervous system • renin-angiotensin system • metabolism

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