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1 Dalton Cardiovascular Reseach Center, Department of Biomedical Sciences and the National Center for Gender Physiology, University of Missouri-Columbia, Columbia, Missouri, USA
* To whom correspondence should be addressed. E-mail: HayM{at}missouri.edu.
Sex has an important influence on blood pressure (BP) regulation. There is increasing evidence that sex hormones interfere with the renin-angiotensin system. Thus, the purpose of this study was to determine if there are sex differences in the development of Angiotensin II (Ang II) induced hypertension in conscious male and female mice. Aortic BP and heart rate (HR) were measured in conscious, freely moving animals with the use of telemetry implants. Ang II (800 ng/kg/min) was delivered via osmotic pump implanted subcutaneously. The results obtained are as follows. Baseline BP in male and female mice were similar. Chronic systemic infusion of Ang II induced a greater increase in BP in male (35.1±5.7 mmHg) than in female mice (7.2±2.0 mmHg). Gonadectomy attenuated Ang II induced hypertension in male mice (15.2±2.4 mmHg) and augmented it in female mice (23.1±1.0 mmHg). Baseline HR was significantly higher in females relative to males (630.1 ± 7.9 bpm vs 544.8 ± 16.2 bpm). In females, Ang II infusion significantly decreased HR. However, the increase in BP with Ang II did not result in the expected decrease in HR in either intact males or the gonadectomized mice. Moreover, the slope of the baroreflex bradycardia to phenylephrine was blunted in males (-5.6±0.3 to -2.9±0.5) but not in females (-6.5±0.5 to -5.6± 0.3) during infusion of Ang II, suggesting that in male mice, infusion of Ang II results in a resetting of the baroreflex control of HR. Ganglionic blockade resulted in greater reduction in BP on day 7 after Ang II infusion in males compared to females (-61.0 ± 8.9 vs -36.6± 6.6 mmHg), suggesting an increased contribution of sympathetic nerve activity in the maintenance of arterial BP in the males. Together, these data indicate that there are sex differences in the development of chronic Ang II-induced hypertension in conscious mice and that females may be protected from the increases in BP induced by Ang II.
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