title: Sex-Specific Effect of Endothelin in the Blood Pressure Response to Acute Angiotensin II in Growth-Restricted Rats.
abstract: The renal endothelin system contributes to sex differences in blood pressure with males demonstrating greater endothelin type-A receptor-mediated responses relative to females. Intrauterine growth restriction programs hypertension and enhance renal sensitivity to acute angiotensin II in male growth-restricted rats. Endothelin is reported to work synergistically with angiotensin II. Thus, this study tested the hypothesis that endothelin augments the blood pressure response to acute angiotensin II in male growth-restricted rats. Systemic and renal hemodynamics were determined in response to acute angiotensin II (100 mg/kg per minute for 30 minutes) with and without the endothelin type-A receptor antagonist, Atrasentan (ABT-627; 10 ng/kg per minute for 30 minutes), in rats pretreated with enalapril (250 mg/L for 1 week) to normalize the endogenous renin-angiotensin system. Endothelin type-A receptor blockade reduced angiotensin II-mediated increases in blood pressure in male control and male growth-restricted rats. Endothelin type-A receptor blockade also abolished hyper-responsiveness to acute angiotensin II in male growth-restricted rats. Yet, blood pressure remained significantly elevated above baseline after endothelin type-A receptor blockade, suggesting that factors in addition to endothelin contribute to the basic angiotensin II-induced pressor response in male rats. We also determined sex-specific effects of endothelin on acute angiotensin II-mediated hemodynamic responses. Endothelin type-A receptor blockade did not reduce acute angiotensin II-mediated increases in blood pressure in female control or growth-restricted rats, intact or ovariectomized. Thus, these data suggest that endothelin type-A receptor blockade contributes to hypersensitivity to acute angiotensin II in male growth-restricted rats and further supports the sex-specific effect of endothelin on blood pressure.
authors.affiliation: Department of Pediatrics (N.B.O.), Department of Physiology and Biophysics (S.I., N.B.O., E.V., T.P.R., B.T.A.), and the Center for Developmental Disorders Research (S.I., N.B.O., B.T.A.), University of Mississippi Medical Center, Jackson.
authors.forename: Suttira
authors.initials: S
authors.lastname: Intapad
authors.affiliation: Department of Pediatrics (N.B.O.), Department of Physiology and Biophysics (S.I., N.B.O., E.V., T.P.R., B.T.A.), and the Center for Developmental Disorders Research (S.I., N.B.O., B.T.A.), University of Mississippi Medical Center, Jackson.
authors.forename: Norma B
authors.initials: NB
authors.lastname: Ojeda
authors.affiliation: Department of Pediatrics (N.B.O.), Department of Physiology and Biophysics (S.I., N.B.O., E.V., T.P.R., B.T.A.), and the Center for Developmental Disorders Research (S.I., N.B.O., B.T.A.), University of Mississippi Medical Center, Jackson.
authors.forename: Elliott
authors.initials: E
authors.lastname: Varney
authors.affiliation: Department of Pediatrics (N.B.O.), Department of Physiology and Biophysics (S.I., N.B.O., E.V., T.P.R., B.T.A.), and the Center for Developmental Disorders Research (S.I., N.B.O., B.T.A.), University of Mississippi Medical Center, Jackson.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Royals
authors.affiliation: Department of Pediatrics (N.B.O.), Department of Physiology and Biophysics (S.I., N.B.O., E.V., T.P.R., B.T.A.), and the Center for Developmental Disorders Research (S.I., N.B.O., B.T.A.), University of Mississippi Medical Center, Jackson. balexander@umc.edu.
authors.forename: Barbara T
authors.initials: BT
authors.lastname: Alexander
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000077868:Atrasentan; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D004656:Enalapril / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism / Q000652:urine; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D010052:Ovariectomy; D011247:Pregnancy; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D044022:Receptor, Endothelin A / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D000804:Angiotensin II; D004656:Enalapril; D000077868:Atrasentan
keywords: angiotensin II; blood pressure; endothelins; renin–angiotensin system; sex characteristics