title: Nitric oxide synthase-mediated blood pressure regulation in obese melanocortin-4 receptor-deficient pregnant rats.
abstract: Although obesity increases the risk for hypertension in pregnancy, the mechanisms responsible are unknown. Increased nitric oxide (NO) production results in vasodilation and reduced blood pressure during normal pregnancy in lean rats; however, the role of NO is less clear during obese pregnancies. We examined the impact of obesity on NO synthase (NOS)-mediated regulation of blood pressure during pregnancy by testing the hypothesis that NOS activity, expression, and regulation of vascular tone and blood pressure are reduced in obese pregnant rats. At gestational day 19, melanocortin-4 receptor (MC4R)-deficient obese rats (MC4R) had greater body weight and fat mass with elevated blood pressure and circulating sFlt-1 levels compared with MC4R pregnant rats. MC4R pregnant rats also had less circulating cGMP levels and reduced total NOS enzymatic activity and expression in mesenteric arteries. Despite decreased biochemical measures of NO/NOS in MC4R rats, NOS inhibition enhanced vasoconstriction only in mesenteric arteries from MC4R rats, suggesting greater NOS-mediated tone. To examine the role of NOS on blood pressure regulation in obese pregnant rats, MC4R and MC4R pregnant rats were administered the nonselective NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 100 mg/l) from gestational day 14 to 19 in drinking water. The degree by which l-NAME raised blood pressure was similar between obese and lean pregnant rats. Although MC4R obese pregnant rats had elevated blood pressure associated with reduced total NOS activity and expression, they had enhanced NOS-mediated attenuation of vasoconstriction, with no evidence of alterations in NOS-mediated regulation of blood pressure.
authors.affiliation: Department of Surgery, The University of Mississippi Medical Center, Jackson, Mississippi; fspradley@umc.edu.|Department of Physiology and Biophysics, The University of Mississippi Medical Center, Jackson, Mississippi.|Cardiovascular-Renal Research Center, The University of Mississippi Medical Center, Jackson, Mississippi.|Women's Health Research Center, The University of Mississippi Medical Center, Jackson, Mississippi; and.
authors.forename: Frank T
authors.initials: FT
authors.lastname: Spradley
authors.affiliation: Department of Pharmacology and Toxicology, The University of Mississippi Medical Center, Jackson, Mississippi.|Cardiovascular-Renal Research Center, The University of Mississippi Medical Center, Jackson, Mississippi.|Women's Health Research Center, The University of Mississippi Medical Center, Jackson, Mississippi; and.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Sasser
authors.affiliation: Department of Physiology, Augusta University, Augusta, Georgia.
authors.forename: Jacqueline B
authors.initials: JB
authors.lastname: Musall
authors.affiliation: Department of Physiology, Augusta University, Augusta, Georgia.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Sullivan
authors.affiliation: Department of Physiology and Biophysics, The University of Mississippi Medical Center, Jackson, Mississippi.|Cardiovascular-Renal Research Center, The University of Mississippi Medical Center, Jackson, Mississippi.|Women's Health Research Center, The University of Mississippi Medical Center, Jackson, Mississippi; and.
authors.forename: Joey P
authors.initials: JP
authors.lastname: Granger
mesh_terms: D000818:Animals; D001794:Blood Pressure; D005260:Female; D006973:Hypertension / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009765:Obesity / Q000503:physiopathology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D051381:Rats; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics / Q000378:metabolism*; D014664:Vasodilation
chemical_list: D044105:Receptor, Melanocortin, Type 4; C000613745:melanocortin receptor type 4, rat; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
keywords: MC4R; hypertension; l-NAME; preeclampsia; women’s health