title: Gender differences in response to acute and chronic angiotensin II infusion: a translational approach.
abstract: Women with renal disease progress at a slower rate to end stage renal disease than men. As angiotensin II has both hemodynamic and direct renal effects, we hypothesized that the female protection may result from gender differences in responses to angiotensin II. Therefore, we studied gender differences in response to angiotensin II, during acute (human) and chronic (rats) angiotensin II administration. In young healthy men (n = 18) and women (n = 18) we studied the responses of renal hemodynamics ((125)I-iothalamate and (131)I-Hippuran) and blood pressure to graded angiotensin II infusion (0.3, 1.0, and 3.0 ng/kg/min for 1 h). Men had increased responses of diastolic blood pressure (P = 0.01), mean arterial pressure (P = 0.05), and a more pronounced decrease in effective renal plasma flow (P = 0.009) than women. We measured the changes in proteinuria and blood pressure in response to chronic administration (200 ng/kg/min for 3 weeks) of angiotensin II in rats. Male rats had an increased response of proteinuria compared with females (GEE analysis, P = 0.001). Male, but not female, angiotensin II-treated rats had increased numbers of renal interstitial macrophages compared to sham-treated rats (P < 0.001). In conclusion, gender differences are present in the response to acute and chronic infusion of angiotensin II. Difference in angiotensin II sensitivity could play a role in gender differences in progression of renal disease.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University of Groningen University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Tsjitske J
authors.initials: TJ
authors.lastname: Toering
authors.affiliation: Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Anne Marijn
authors.initials: AM
authors.lastname: van der Graaf
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University of Groningen University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Folkert W
authors.initials: FW
authors.lastname: Visser
authors.affiliation: Department of Clinical Pharmacology, University of Groningen University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Buikema
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University of Groningen University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.affiliation: Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Marijke M
authors.initials: MM
authors.lastname: Faas
authors.affiliation: Department of Obstetrics & Gynaecology, University of Groningen University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: A Titia
authors.initials: AT
authors.lastname: Lely
keywords: Angiotensin II; proteinuria; renal damage; renal hemodynamics; sex