Protective actions of estrogen on angiotensin II-induced hypertension: Role of central nitric oxide

Baojian Xue, Minati Singh, Fang Guo, Meredith Hay, Alan Kim Johnson

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


The present study tested the hypotheses that 1) nitric oxide (NO) is involved in attenuated responses to ANG II in female mice, and 2) there is differential expression of neuronal NO synthase (nNOS) in the subfornical organ (SFO) and paraventricular nucleus (PVN) in response to systemic infusions of ANG II in males vs. females. Aortic blood pressure (BP) was measured in conscious mice with telemetry implants. NG-nitro-L-arginine methyl ester (L-NAME; 100 μg·kg.-1day-1), an inhibitor of NOS, was administrated into the lateral cerebral ventricle for 14 days before and during ANG II pump implantation. Central infusion of L-NAME augmented the pressor effects of systemic ANG II in females (Δ21.5 ± 2.2 vs. Δ9.2 ± 1.5 mmHg) but not in males (Δ29.4 ± 2.5 vs. Δ30.1 ± 2.5 mmHg). Central administration of N5-(1- imino-3-butenyl)-L-ornithine (L-VNIO), a selective nNOS inhibitor, also significantly potentiated the increase in BP induced by ANG II in females (Δ17.5 ± 3.2 vs. Δ9.2 ± 1.5 mmHg). In gonadectomized mice, central L-NAME infusion did not affect the pressor response to ANG II in either males or females. Ganglionic blockade after ANG II infusion resulted in a greater reduction in BP in central L-NAME- or L-VNIO-treated females compared with control females. Western blot analysis of nNOS protein expression indicated that levels were ∼12-fold higher in both the SFO and PVN of intact females compared with those in intact males. Seven days of ANG II treatment resulted in a further increase in nNOS protein expression only in intact females (PVN, to ∼51-fold). Immunohistochemical studies revealed colocalization of nNOS and estrogen receptors in the SFO and PVN. These results suggest that NO attenuates the increase in BP induced by ANG II through reduced sympathetic outflow in females and that increased nNOS protein expression associated with the presence of female sex hormones plays a protective role against ANG II-induced hypertension in female mice.

Original languageEnglish (US)
Pages (from-to)H1638-H1646
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number5
StatePublished - Nov 2009


  • Blood pressure
  • Nitric oxide/nitric oxide synthase
  • Sex hormone

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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