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

Abstract

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, 11␤-hydroxysteroid dehydrogenase type 2 (11␤HSD2), 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. 11␤HSD2 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 11␤HSD2 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. (Endocrinology 145: 4286 -4291, 2004)

Renin Enhancer Is Critical for Control of Renin Gene Expression and Cardiovascular Function

“…The average value of the transfer gain in the frequency band between 0.3 and 0.5 Hz was used as the estimate of the baroreflex sensitivity (26). Other frequency bands included in the analysis were low frequency (0.08 -0.3 Hz) and high frequency (0.5-1 Hz), and the total power was calculated between 0 and 1 Hz (27). During the same period, the spontaneous baroreflex slope was calculated as the slope of the linear regression lines between the SAP and HR, with a delay of 0 -6 heartbeats, using the sequence technique (28,29).…”

Optimal frequency ranges for extracting information on cardiovascular autonomic control from the blood pressure and pulse interval spectrograms in mice

“…This technique has been successfully applied to rats (4, 25) and more recently to mice (5,19,29,42). Several authors have already applied spectral analysis to mice BP and HR recordings obtained by telemetry (7,12,32,35,40,42) and previously by the conventional method of an exteriorized arterial catheter connected to pressure transducers (14,19,21,23,34,43). The responses to pharmacological blockade of the autonomic receptors support the view that spectral analysis of autonomic cardiovascular variability may be transferable to mice.…”

The role of sex in cardiac function and diseaseThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigator's Forum.

“…Fatty acid oxidation in the liver is impaired in these mice, concomitant with hepatic steatosis (Nemoto et al 2000); however, it is unknown whether fatty acid oxidation in the heart is similarly affected. While direct effects in the heart have yet to be reported, these mice exhibited increased adiposity (Jones et al 2000), progressive insulin resistance (Takeda et al 2003), impaired endothelium-dependent relaxation of aortic smooth muscle (Kimura et al 2003), reduced proliferation and increased apoptosis of vascular smooth muscle (Ling et al 2004), and reduced blood pressure and baroreflex sensitivity (Head et al 2004). These defects play significant roles in the development of cardiovascular diseases such as atherosclerosis and diabetic cardiomyopathy, thus defects in aromatase function in humans may be important in the susceptibility and progression of these diseases.…”