Nitric oxide synthase upregulation and the predelivery blood pressure decrease in spontaneously hypertensive rats

J Hypertens. 2002 Feb;20(2):255-61. doi: 10.1097/00004872-200202000-00015.

Abstract

Objective: The pregnant spontaneously hypertensive rat (SHR) exhibits a decrease in arterial blood pressure shortly before delivery; however, the mechanisms are unknown. Nitric oxide may be involved.

Design: Blood pressure in stroke-prone SHR (SHRSP) and Wistar-Kyoto control rats (WKY) was telemetrically measured. Four groups were studied: pregnant and non-pregnant WKY and SHRSP rats, respectively. Mean blood pressure in pregnant SHRSP rats decreased from 148 +/- 2 mmHg at conception to 120 +/- 4 mmHg at day 15, compared to 112 +/- 1 mmHg in pregnant WKY rats. At delivery, we determined the vasodilatory responses of isolated preconstricted aortic strips.

Results: Vasodilatory responses from late-term SHRSP rats were significantly greater following acetylcholine than either those from non-pregnant SHRSP or pregnant and non-pregnant WKY rats (acetylcholine IC50: 5, 22.8, 398, 1000 nmol/l, respectively), while contractile responses to increasing doses of norepinephrine were not different. Similar results were obtained with substance P. Indomethacin had no effect on the relaxation responses. Relaxation in response to sodium nitroprusside was not different in the groups. Western blot analysis showed that endothelial nitric oxide synthase (eNOS) levels were significantly increased in the pregnant SHRSP vessels compared to non-pregnant SHRSP, pregnant WKY, and non-pregnant WKY vessels.

Conclusion: Increased NOS may explain the blood pressure decrease during late pregnancy in genetically hypertensive rats.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology
  • Female
  • Muscle Relaxation / drug effects
  • Muscle Relaxation / physiology
  • Nitric Oxide Synthase / drug effects
  • Nitric Oxide Synthase / physiology*
  • Norepinephrine / pharmacology
  • Pregnancy / physiology*
  • Rats
  • Rats, Inbred SHR / physiology*
  • Rats, Inbred WKY
  • Time Factors
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*
  • Vasoconstrictor Agents / pharmacology
  • Vasodilator Agents / pharmacology

Substances

  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Nitric Oxide Synthase
  • Acetylcholine
  • Norepinephrine