Sex differences in the enhanced responsiveness to acute angiotensin II in growth-restricted rats: role of fasudil, a Rho kinase inhibitor

作者：Ojeda Norma B; Royals Thomas P; Alexander Barbara T^*

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2013, 304(7): F900-F907.

DOI：10.1152/ajprenal.00687.2012

• sex differences
• intrauterine growth restriction
• developmental programmed hypertension
• angiotensin II
• Rho kinase

Ojeda NB, Royals TP, Alexander BT. Sex differences in the enhanced responsiveness to acute angiotensin II in growth-restricted rats: role of fasudil, a Rho kinase inhibitor. Am J Physiol Endocrinol Metab 304: F900-F907, 2013. First published January 23, 2013; doi:10.1152/ajprenal.00687.2012.-This study tested the hypothesis that Rho kinase contributes to the enhanced pressor response to acute angiotensin II in intact male growth-restricted and gonadectomized female growth-restricted rats. Mean arterial pressure (MAP) and renal function were determined in conscious animals pretreated with enalapril (250 mg/l in drinking water) for 1 wk to block the endogenous renin-angiotensin system and normalize blood pressure (baseline). Blood pressure and renal hemodynamics did not differ at baseline. Acute Ang II (100 ng.kg(-1).min(-1)) induced a greater increase in MAP and renal vascular resistance and enhanced reduction in glomerular filtration rate in intact male growth-restricted rats compared with intact male controls (P %26lt; 0.05). Cotreatment with the Rho kinase inhibitor fasudil (33 mu g.kg(-1).min(-1)) significantly attenuated these hemodynamic changes (P %26lt; 0.05), but it did not abolish the differential increase in blood pressure above baseline, suggesting that the impact of intrauterine growth restriction on blood pressure in intact male growth-restricted rats is independent of Rho kinase. Gonadectomy in conjunction with fasudil returned blood pressure back to baseline in male growth-restricted rats, and yet glomerular filtration rate remained significantly reduced (P %26lt; 0.05). Thus, these data suggest a role for enhanced renal sensitivity to acute Ang II in the developmental programming of hypertension in male growth-restricted rats. However, inhibition of Rho kinase had no effect on the basal or enhanced increase in blood pressure induced by acute Ang II in the gonadectomized female growth-restricted rat. Therefore, these studies suggest that Rho kinase inhibition exerts a sex-specific effect on blood pressure sensitivity to acute Ang II in growth-restricted rats.

• 出版日期2013-4