The role of the AT1 receptor antagonist on renal hemodynamic responses to angiotensin 1-7 in acute sympathectomized male and female rats

Abstract

Introduction: The sympathetic nervous system and the renin-angiotensin system (RAS) are the most pivotal vasoactive systems in regulating renal hemodynamics. The main objective of this study was to determine the role of the angiotensin II (Ang II) type 1 receptor (AT1R) antagonist on renal hemodynamic responses to Ang 1-7 infusion in innervated and denervated male and female rats. Methods: Male and female Wistar rats underwent unilateral nephrectomy. Four weeks later, they were divided into two groups: innervated and acutely denervated groups. Subsequently, the anesthetized and catheterized rats in both groups were treated with saline as a vehicle and losartan infusion. Mean arterial pressure (MAP), renal blood flow (RBF), renal perfusion pressure (RPP), and renal vascular resistance (RVR) responses to Ang 1-7 (100, 300, and 1000 ng kg-1 min-1 ) were then measured at controlled RPP. Results: Basal MAP, RPP, RBF, and RVR did not show significant differences between the intact and denervated groups. Losartan significantly decreased MAP, RPP, and RVR in both innervated and denervated male and female rats (P<0.001), while RBF increased only in innervated and denervated female rats (P<0.004). However, following Ang 1-7 administration, the RBF response to Ang 1-7 infusion differed significantly between intact and denervated male rats treated with losartan (P<0.04). This response was not observed in female rats. Conclusion: These data suggest a synergistic effect of losartan and Ang 1-7 on increased RBF in the presence of renal sympathetic nerves in male rats.