Estrogen protects transgenic hypertensive rats by shifting the vasoconstrictor-vasodilator balance of RAS

Am J Physiol. 1997 Dec;273(6):R1908-15. doi: 10.1152/ajpregu.1997.273.6.R1908.


In pursuit of the hypothesis that estrogen shifts the vasoconstrictor-vasodilator balance of the renin-angiotensin system, we investigated the cardiovascular responses to administration of angiotensin-(1-7) [ANG-(1-7)] and angiotensin II (ANG II) in female transgenic (mRen2)27-positive [Tg(+)] and -negative [Tg(-)] rats in the presence and absence of 3 wk of estrogen replacement therapy. Fifty-three female Tg(-) and Tg(+) rats were oophorectomized and received either 17 beta-estradiol (1.5 mg/rat s.c. for 3 wk) or vehicle. At the end of 3 wk of estrogen treatment, mean blood pressure was lowered in freely moving chronically cannulated Tg(+) (159 +/- 4 vs. 145 +/- 5 mmHg, P < 0.05) and Tg(-) (119 +/- 4 vs. 108 +/- 2 mmHg, P < 0.05) rats. Moreover, the magnitude of the depressor component of the biphasic response to ANG-(1-7) was significantly enhanced in estrogen-treated Tg(+) rats, whereas the pressor component to ANG-(1-7) was attenuated in both Tg(+) and Tg(-) rats. Estrogen replacement significantly attenuated the pressor response to ANG II in both Tg(+) and Tg(-) rats. In addition, estrogen replacement therapy significantly reduced plasma ANG-converting enzyme activity in association with a reduction in circulating levels of ANG II. Tissue levels (kidney and aorta) of ANG-converting enzyme were also reduced with chronic estrogen replacement therapy. On the other hand, estrogen augmented the levels of plasma ANG-(1-7) in Tg(+) animals. Plasma renin activity was unchanged with estrogen treatment. These findings provide the first evidence demonstrating that estrogen is protective against hypertension, possibly by amplifying the vasodilator contributions of ANG-(1-7), while reducing the formation and vasoconstrictor actions of ANG II.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin I
  • Angiotensin II / blood
  • Angiotensin II / pharmacology
  • Animals
  • Animals, Genetically Modified
  • Aorta, Thoracic / enzymology
  • Blood Pressure / drug effects
  • Estradiol / therapeutic use*
  • Estrogen Replacement Therapy*
  • Female
  • Hypertension / drug therapy*
  • Hypertension / genetics
  • Hypertension / physiopathology*
  • Kidney / enzymology
  • Mice
  • Models, Cardiovascular
  • Muscle, Smooth, Vascular / enzymology
  • Ovariectomy
  • Peptide Fragments / pharmacology
  • Peptidyl-Dipeptidase A / blood
  • Peptidyl-Dipeptidase A / metabolism
  • Rats
  • Renin / biosynthesis
  • Renin / genetics*
  • Renin-Angiotensin System / physiology*
  • Vasoconstriction / physiology*
  • Vasodilation / physiology*


  • Peptide Fragments
  • Angiotensin II
  • Estradiol
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • Renin
  • angiotensin I (1-7)