title: Blood pressure and renal hemodynamic responses to acute angiotensin II infusion are enhanced in a female mouse model of systemic lupus erythematosus.
abstract: Inflammation and immune system dysfunction contributes to the development of cardiovascular and renal disease. Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that carries a high risk for both renal and cardiovascular disease. While hemodynamic changes that may contribute to increased cardiovascular risk have been reported in humans and animal models of SLE, renal hemodynamics have not been widely studied. The renin-angiotensin system (RAS) plays a central role in renal hemodynamic control, and although RAS blockade is a common therapeutic strategy, the role of RAS in hemodynamic function during SLE is not clear. This study tested whether mean arterial pressure (MAP) and renal hemodynamic responses to acute infusions of ANG II in anesthetized animals were enhanced in an established female mouse model of SLE (NZBWF1). Baseline MAP was not different between anesthetized SLE and control (NZWLacJ) mice, while renal blood flow (RBF) was significantly lower in mice with SLE. SLE mice exhibited an enhanced pressor response and greater reduction in RBF after ANG II infusion. An acute infusion of the ANG II receptor blocker losartan increased RBF in control mice but not in mice with SLE. Renin and ANG II type 1 receptor expression was significantly lower, and ANG II type 2 receptor expression was increased in the renal cortex from SLE mice compared with controls. These data suggest that there are fewer ANG II receptors in the kidneys from mice with SLE but that the existing receptors exhibit an enhanced sensitivity to ANG II.
authors: Department of Physiology and Biophysics and Center for Excellence in Cardiovascular Renal Research, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
authors: Marcia
authors: M
authors: Venegas-Pont
authors: Keisa W
authors: KW
authors: Mathis
authors: Radu
authors: R
authors: Iliescu
authors: William H
authors: WH
authors: Ray
authors: Porter H
authors: PH
authors: Glover
authors: Michael J
authors: MJ
authors: Ryan
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure; D004195:Disease Models, Animal; D005260:Female; D006973:Hypertension / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008814:Mice, Inbred NZB; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D012079:Renal Circulation; D014655:Vascular Resistance; D014661:Vasoconstriction
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D019808:Losartan