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

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 and renal function were determined in conscious animals pretreated with enalapril (250mg/l in drinking water) for one week 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 (100ng/kg/min) induced a greater increase in mean arterial pressure (MAP) and renal vascular resistance and enhanced reduction in glomerular filtration rate in intact male growth-restricted rats compared to intact male control (P<0.05). Co-treatment with the Rho-kinase inhibitor, fasudil (33ug/kg/min), significantly attenuated these hemodynamic changes (P<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; yet, glomerular filtration rate remained significantly reduced (P<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 ...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research