Role of Bradykinin and Mas Receptor Blockade in Renal Vascular Responses to Angiotensin 1-7 in Adult Female Rats



Saberi S¹ ; Nematbakhsh M^{2, 3} ; Dehghani A⁴ Show Affiliations
Source: Journal of Mazandaran University of Medical Sciences Published:2020

Abstract

Background and purpose: Chronic kidney disease is among the common diseases in the world. Studies show that women are more protected against renal diseases compared to men. On the other hand, vasodilatory axises of renin angiotensin system (angiotensin 1-7 (Ang 1-7)-Mas receptor (MasR)), kallikrein-kinin, and nitric oxide (NO) play key roles in kidney function and circulation in females. Therefore, the purpose of this study was to examine the effect of bradykinin in renal blood flow (RBF) response to Ang 1-7 when MasR was blocked in female rats. Materials and methods: Female Wistar rats were divided into three groups (control, Bradykinine, and Bradykinin + MasR antagonist (A779)). The animals were anesthetized and catheterized in the carotid and femoral arteries and jugular vein to measure mean arterial pressure (MAP), renal perfusion pressure (RPP), and drug administration, respectively. The left kidney was exposed (in situ) and placed in a kidney cup to measure RBF. After the equilibration period, A779 and bradykinin (50 μg/kg/h, 150 μg/kg/h, respectively) were injected and vascular responses to Ang1-7 (100, 300, and 1000 ng kg−1min−1) infusion were determined. At the end of the experiment, blood samples were collected for measuring the level of nitrite. Results: The MAP and RPP were not significantly different between the three groups. Bradykinin exhibited vasodilatory effect on RBF in response to Ang 1-7 in female rats, however, A779 administration increased RBF at low dose of Ang 1-7(Pdose=0.001). The serum level of nitrite significantly decreased when the MasR was blocked (P= 0.04). Conclusion: Bradykinin enhanced RBF response to Ang 1-7 infusion. The effect of bradykinin on RBF response to Ang 1-7 may be modulated via the NO pathway. Interaction of these factors might help to broaden our vision for treatment strategy in future. © 2020, Mazandaran University of Medical Sciences. All rights reserved.