CALL FOR PAPERS Sex Differences in Renal and Cardiovascular Function: Physiology and Pathophysiology Testosterone contributes to marked elevations in mean arterial pressure in adult male intrauterine growth restricted offspring
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چکیده
Ojeda, Norma B., Daniela Grigore, Licy L. Yanes, Radu Iliescu, Elliot B. Robertson, Huimin Zhang, and Barbara T. Alexander. Testosterone contributes to marked elevations in mean arterial pressure in adult male intrauterine growth restricted offspring. Am J Physiol Regul Integr Comp Physiol 292: R758–R763, 2007. First published August 17, 2006; doi:10.1152/ajpregu.00311.2006.—Our laboratory uses a model of intrauterine growth restriction (IUGR) induced by placental insufficiency in the rat to examine the developmental origins of adult disease. In this model only male IUGR offspring remain hypertensive in adulthood, revealing sex-specific differences. The purpose of this study was to determine whether testosterone with participation of the renin-angiotensin system (RAS) contributes to hypertension in adult male IUGR offspring. At 16 wk of age a significant increase in testosterone (346 34 vs. 189 12 ng/dl, P 0.05) was associated with a significant increase in mean arterial pressure (MAP) measured by telemetry in IUGR offspring (147 1 vs. 125 1 mmHg, P 0.05, IUGR vs. control, respectively). Gonadectomy (CTX) at 10 wk of age significantly reduced MAP by 16 wk of age in IUGR offspring (124 2 mmHg, P 0.05 vs. intact IUGR) but had no effect in control (125 2 mmHg). A significant decrease in MAP in intact IUGR (111 3 mmHg, P 0.05 vs. untreated intact IUGR) and castrated IUGR (110 4 mmHg, P 0.05 vs. untreated CTX IUGR) after treatment with enalapril for 2 wk suggests a role for RAS involvement. However, the decrease in blood pressure in response to enalapril was greater in intact IUGR ( 36 1 mmHg, P 0.05) compared with CTX IUGR ( 15 2 mmHg), indicating an enhanced response to RAS blockade in the presence of testosterone. Thus these results suggest that testosterone plays a role in modulating hypertension in adult male IUGR offspring with participation of the RAS.
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