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Aromatase-Deficient (ArKO) Mice Have Reduced Blood Pressure and Baroreflex Sensitivity

Baker Heart Research Institute (G.A.H., V.R.O., Z.S.K.), Melbourne, Victoria 8008, Australia; and Prince Henry’s Institute for Medical Research (M.E.J., E.R.S.), Clayton, Victoria 3168, Australia

Address all correspondence and requests for reprints to: Dr. Geoffrey A. Head, Baker Heart Research Institute, P.O. Box 6492, St. Kilda Road Central, Melbourne, Victoria 8008, Australia. E-mail: geoff.head{at}baker edu.au.

Aromatase-deficient (ArKO) mice are deficient in estrogens due to deletion of the aromatase gene. We hypothesized that there may be changes in the cardiovascular system of ArKO mice because of evidence linking estrogens with improved cardiovascular outcomes and the induction of the glucocorticoid-metabolizing enzyme, 11ß-hydroxysteroid dehydrogenase type 2 (11ßHSD2), gene in the kidney, which is important for the regulation of blood pressure (BP). BP and baroreflex sensitivity (BRS) in female conscious ArKO mice were compared with those in age- and weight-matched wild-type (WT) mice. Power spectral analysis was used to determine cardiovascular variability and BRS. Although systolic BP was similar in the two groups, diastolic and mean BPs were lower in the ArKO mice (–6.3 ± 1.9 and –4.6 ± 2.1 mm Hg, respectively). Heart rate (HR) was greater in the ArKO mice (+36 ± 6 beats/min). The mean BP in WT mice was 105 mm Hg, and the HR was 481 beats/min. In the autonomic frequency range, BP variability was 74% greater, and HR variability was only 26% that in WT mice. The BRS of ArKO mice was 46% of the value observed in WT mice. 11ßHSD2 levels were unaltered in ArKO mice, except in the kidney, where they were only 10% of WT levels. Estradiol administration to ArKO mice restored renal 11ßHSD2 to WT levels. The results show that ArKO mice have lower diastolic BP, but increased BP variability, perhaps due to an impaired BRS. Thus, aromatase activity is critical for normal autonomic control of the heart and, hence, for reducing the deleterious effects of high BP variability.

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