Journal of the American Society of Nephrology
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Published ahead of print on February 7, 2007
J Am Soc Nephrol 18: 944-951, 2007
© 2007 American Society of Nephrology
doi: 10.1681/ASN.2006091026

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Hemodynamics and Vascular Regulation

Insulin Induces Renal Vasodilation, Increases Plasma Renin Activity, and Sensitizes the Renal Vasculature to Angiotensin Receptor Blockade in Healthy Subjects

Todd S. Perlstein*,{dagger}, Marie Gerhard-Herman{dagger}, Norman K. Hollenberg{ddagger}, Gordon H. Williams* and Abraham Thomas*,§

* Division of Endocrinology, Diabetes and Hypertension, and {dagger} Division of Cardiology, Department of Medicine, and the {ddagger} Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; and § Division of Endocrinology and Metabolism, Henry Ford Hospital, Detroit, Michigan

Address correspondence to: Dr. Todd S. Perlstein, Brigham and Women’s Hospital, Cardiovascular Division, 75 Francis Street, A Building, Boston, MA 02115. Phone: 617-545-7168; Fax: 617-264-5265; E-mail: tperlstein{at}partners.org

Received for publication September 20, 2006. Accepted for publication January 1, 2007.

Insulin stimulates the renin-angiotensin system and induces renal vasodilation. The relationship between these opposing influences of insulin on renal vascular tone has not been explored. A hyperinsulinemic euglycemic clamp and sham insulin clamp each of 270 min duration were performed in 15 healthy individuals during high sodium balance. An angiotensin receptor blocker was administered at time 180 min. Renal plasma flow and plasma renin activity were measured serially. The response to insulin or sham insulin infusion was defined as the change from time 0 to 180 min; the response to angiotensin receptor blockade (ARB) was defined as the change from time 180 to 270 min. Insulin infusion increased plasma renin activity (P < 0.01) and renal plasma flow (P < 0.01); the latter effect plateaued by time 150 min. ARB caused a greater vasodilator response during insulin infusion compared with during sham insulin infusion (P = 0.02). Increasing renin response to insulin predicted blunting of the renal vasodilator response to insulin infusion (R2 = 0.36, P = 0.02) and sensitizing of the renal vasodilator response to ARB during insulin infusion (R2 = 0.59, P < 0.01). Insulin-induced activation of the renin-angiotensin system modulates insulin-induced renal vasodilation in healthy individuals. Further studies are warranted to address this balance in states of insulin resistance and the possible implications for the association of insulin resistance with risk for chronic kidney disease.


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