Sex differences in the development of angiotensin II-induced hypertension in conscious mice

Dalton Cardiovascular Research Center, Department of Biomedical Sciences and the National Center for Gender Physiology, University of Missouri-Columbia, Columbia, Missouri Submitted 22 September 2004 ; accepted in final form 22 December 2004 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 whether there are sex differences in the development of ANG II-induced hypertension in conscious male and female mice. We used telemetry implants to measure aortic BP and heart rate (HR) in conscious, freely moving animals. ANG II (800 ng·kg –1 ·min –1 ) was delivered via an osmotic pump implanted subcutaneously. Our results showed baseline BP in male and female mice to be 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 vs. 544.8 ± 16.2 beats/min). 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 male or 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 with females (–61.0 ± 8.9 vs. –36.6 ± 6.6 mmHg), suggesting an increased contribution of sympathetic nerve activity in arterial BP maintenance in male mice. 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. cardiovascular disease; sex hormones Address for reprint requests and other correspondence: M. Hay, Dalton Cardiovascular Research Center, Research Park, Univ. of Missouri Columbia, MO 65211 (E-mail: haym{at}missouri.edu )