PMID- 28391290 OWN - NLM STAT- MEDLINE DCOM- 20180212 LR - 20181113 IS - 1941-7225 (Electronic) IS - 0895-7061 (Print) IS - 0895-7061 (Linking) VI - 30 IP - 3 DP - 2017 Mar 1 TI - Role of Nitric Oxide Synthase on Blood Pressure Regulation and Vascular Function in Pregnant Rats on a High-Fat Diet. PG - 240-248 LID - 10.1093/ajh/hpw153 [doi] AB - BACKGROUND: While obesity is a leading risk factor for preeclampsia, the mechanisms whereby obese women are more susceptible to pregnancy-induced hypertension are unclear. As high-fat diet (HFD) is an important contributor to the development of obesity, we tested the hypothesis that pregnant rats on HFD have hypertension and endothelial dysfunction due to reduced nitric oxide synthase (NOS). METHODS: Twelve-week-old Sprague-Dawley female rats were fed normal diet (ND, 13% fat kcal) or HFD (40% fat kcal) for 9 weeks. Timed-pregnant rats were then generated and the effect of HFD on mean arterial blood pressure (MAP) and vascular function was assessed on gestational day (GD) 19. RESULTS: MAP was not different between HFD and ND pregnant rats. Intriguingly, sensitivity to acetylcholine-induced endothelium-dependent vasorelaxation was enhanced in small mesenteric arteries of HFD dams compared to ND controls (logEC50 -7.9 +/- 0.3 vs. -6.7 +/- 0.3 M; P < 0.05). Additionally, HFD dams exhibited higher mesenteric artery expression of NOS3 and plasma levels of NO metabolites than ND controls (1738.0 +/- 316.4 vs. 1094.0 +/- 82.5 pg/mg and 72.5 +/- 8.7 vs. 39.7 +/- 4.5 microM, respectively; both P < 0.05). Further, to determine the role of NOS in modulating blood pressure in HFD pregnant rats, animals were treated with the nonselective inhibitor Nomega-Nitro-l-arginine methyl ester hydrochloride (100 mg/l, drinking water) from GD 14 to 19. It was found that NOS inhibition increased MAP equally in HFD and ND groups. CONCLUSIONS: Contrary to our initial hypothesis, HFD dams were normotensive and presented increased endothelial function and NO/NOS3 levels. This enhanced NOS-mediated vascular function does not appear to have a major impact on blood pressure regulation of HFD-fed pregnant rats. CI - (c) American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com FAU - Palei, Ana C AU - Palei AC AD - Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA. AD - Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi, USA. FAU - Spradley, Frank T AU - Spradley FT AD - Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA. AD - Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi, USA. AD - Department of Surgery, University of Mississippi Medical Center, Jackson, Mississippi, USA. FAU - Granger, Joey P AU - Granger JP AD - Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA. AD - Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi, USA. LA - eng GR - P01 HL051971/HL/NHLBI NIH HHS/United States GR - P20 GM104357/GM/NIGMS NIH HHS/United States GR - T32 HL105324/HL/NHLBI NIH HHS/United States PT - Journal Article PL - United States TA - Am J Hypertens JT - American journal of hypertension JID - 8803676 RN - 0 (Vasodilator Agents) RN - EC 1.14.13.39 (NOS3 protein, human) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) RN - N9YNS0M02X (Acetylcholine) SB - IM MH - Acetylcholine/pharmacology MH - Animals MH - Arterial Pressure MH - Blood Pressure/*physiology MH - Blood Vessels/*physiology MH - Diet, High-Fat/*adverse effects MH - Endothelium, Vascular/physiopathology MH - Female MH - Hypertension, Pregnancy-Induced/enzymology MH - Mesenteric Arteries/drug effects MH - Nitric Oxide Synthase/*physiology MH - Nitric Oxide Synthase Type III/biosynthesis/genetics MH - Pregnancy MH - Rats MH - Rats, Sprague-Dawley MH - Vasodilator Agents/pharmacology PMC - PMC5861551 OTO - NOTNLM OT - blood pressure OT - endothelial function OT - high-fat diet OT - hypertension OT - nitric oxide OT - pregnancy. EDAT- 2017/04/10 06:00 MHDA- 2018/02/13 06:00 PMCR- 2018/01/27 CRDT- 2017/04/10 06:00 PHST- 2016/06/27 00:00 [received] PHST- 2016/11/16 00:00 [accepted] PHST- 2017/04/10 06:00 [entrez] PHST- 2017/04/10 06:00 [pubmed] PHST- 2018/02/13 06:00 [medline] PHST- 2018/01/27 00:00 [pmc-release] AID - 2958577 [pii] AID - hpw153 [pii] AID - 10.1093/ajh/hpw153 [doi] PST - ppublish SO - Am J Hypertens. 2017 Mar 1;30(3):240-248. doi: 10.1093/ajh/hpw153.