Role of Nitric Oxide Synthase on Blood Pressure Regulation and Vascular Function in Pregnant Rats on a High-Fat Diet

Am J Hypertens. 2017 Mar 1;30(3):240-248. doi: 10.1093/ajh/hpw153.


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 µM, 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 Nω-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.

Keywords: blood pressure; endothelial function; high-fat diet; hypertension; nitric oxide; pregnancy..

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Arterial Pressure
  • Blood Pressure / physiology*
  • Blood Vessels / physiology*
  • Diet, High-Fat / adverse effects*
  • Endothelium, Vascular / physiopathology
  • Female
  • Hypertension, Pregnancy-Induced / enzymology
  • Mesenteric Arteries / drug effects
  • Nitric Oxide Synthase / physiology*
  • Nitric Oxide Synthase Type III / biosynthesis
  • Nitric Oxide Synthase Type III / genetics
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Vasodilator Agents / pharmacology


  • Vasodilator Agents
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Acetylcholine