1. Interaction of Angiotensin-(1-7) with kinins in the kidney circulation: Role of B 1 receptors.
- Author
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Mendes EP, Ianzer D, Peruchetti DB, Santos RAS, and Vieira MAR
- Subjects
- Animals, Cricetinae, Male, Rats, Angiotensin II analogs & derivatives, CHO Cells, Cricetulus, Kallikrein-Kinin System physiology, Kallikrein-Kinin System drug effects, Kidney metabolism, Kidney drug effects, Kinins metabolism, Proto-Oncogene Mas, Proto-Oncogene Proteins metabolism, Rats, Wistar, Receptors, G-Protein-Coupled metabolism, Renal Circulation drug effects, Renin-Angiotensin System drug effects, Renin-Angiotensin System physiology, Angiotensin I pharmacology, Angiotensin I metabolism, Bradykinin pharmacology, Bradykinin analogs & derivatives, Peptide Fragments pharmacology, Receptor, Bradykinin B1 metabolism, Vascular Resistance drug effects
- Abstract
Changes in renal hemodynamics impact renal function during physiological and pathological conditions. In this context, renal vascular resistance (RVR) is regulated by components of the Renin-Angiotensin System (RAS) and the Kallikrein-Kinin System (KKS). However, the interaction between these vasoactive peptides on RVR is still poorly understood. Here, we studied the crosstalk between angiotensin-(1-7) and kinins on RVR. The right kidneys of Wistar rats were isolated and perfused in a closed-circuit system. The perfusion pressure and renal perfusate flow were continuously monitored. Ang-(1-7) (1.0-25.0 nM) caused a sustained, dose-dependent reduction of relative RVR (rRVR). This phenomenon was sensitive to 10 nM A-779, a specific Mas receptor (MasR) antagonist. Bradykinin (BK) promoted a sustained and transient reduction in rRVR at 1.25 nM and 125 nM, respectively. The transient effect was abolished by 4 μM des-Arg9-Leu8-bradykinin (DALBK), a specific kinin B
1 receptor (B1 R) antagonist. Accordingly, des-Arg9-bradykinin (DABK) 1 μM (a B1 R agonist) increased rRVR. Interestingly, pre-perfusion of Ang-(1-7) changed the sustained reduction of rRVR triggered by 1.25 nM BK into a transient effect. On the other hand, pre-perfusion of Ang-(1-7) primed and potentiated the DABK response, this mechanism being sensitive to A-779 and DALBK. Binding studies performed with CHO cells stably transfected with MasR, B1 R, and kinin B2 receptor (B2 R) showed no direct interaction between Ang-(1-7) with B1 R or B2 R. In conclusion, our findings suggest that Ang-(1-7) differentially modulates kinin's effect on RVR in isolated rat kidneys. These results help to expand the current knowledge regarding the crosstalk between the RAS and KKS complex network in RVR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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