The Effects of Alamandine on the NHE3 Exchanger in in vivo Proximal Tubule of Spontaneously Hypertensive Rats.

Abstract

The action of Alamandine on the NHE3 exchanger contributes to understanding the etiology of hypertension in spontaneously hypertensive rats (SHR) and their controls, Wistar‐Kyoto rats (WKY). Angiotensin‐(1–7) [Ang‐(1–7)], a heptapeptide member of the renin‐angiotensin system, acts in opposition to the vasoconstrictor, proliferative, and profibrotic actions of Angiotensin II (Ang II) in the cardiovascular system and proximal renal tubule. In normotensive Wistar rats, the dose‐dependent biphasic action of Ang‐(1–7) on NHE3 of renal proximal tubular epithelium is also in opposition of the dose‐dependent biphasic action of Ang II. The presently reported effects of Alamandine were similar to those obtained with Ang‐(1–7), including vasodilation, antifibrosis, reduction of blood pressure in spontaneously hypertensive rats and control of cardiovascular functions. This study was designed to determine the effects of Alamandine on reabsorptive bicarbonate flow (JHCO3−) in in vivo middle proximal tubules. This action was evaluated by bicarbonate reabsorption (JHCO3−) of in vivo proximal renal tubules, using microperfusion with H+ ion‐sensitive microelectrodes. By means tail‐cuff plethysmography the mean values of systolic pressure were obtained in WKY [136 ± 1 mmHg (N=15)] and SHR [181± 3 mmHg (N=9)]. In WKY rats, the mean control value of JHCO3− was 2.34 ± 0.13 nmol.cm−2.s−1 (N= 14). Alamandine [10−12 M] in luminally perfused tubules caused a significant decrease of the JHCO3− to 1,10 ± 0,07 nmol.cm−2.s−1 (28); the following perfusions also significantly decreased JHCO3−: Alamandine [10−9 M] to 1.20 ± 0.13 nmol.cm−2.s−1 (22); Alamandine [10−6 M] to 1.58 ± 0,10 nmol.cm−2.s−1 (17). In SHR rats, the mean control value of JHCO3− was 2.31 ± 0.15 nmol.cm−2.s−1 (12). Alamandine [10−12 M] in luminally perfused tubules causes a significant decrease of the JHCO3− to 1.38 ± 0.07 nmol.cm−2.s−1 (18); the following perfusions also significantly decreased JHCO3−: Alamandine [10−9 M] to 1.42 ± 0.16 nmol.cm−2.s−1 (15); Alamandine [10−6 M] to 1.58 ± 0.13 nmol.cm−2.s−1 (20). So, our data are showing that in WKY and SHR rats, the inhibitory dose‐dependent effect of Alamandine on JHCO3−, demonstrates a possible inhibitory beneficial effect of Alamandine in hypertensive rats opposite to the deleterious stimulatory effects of Ang II. It is therefore reasonable to assume that, in the intact animal, the interaction of the opposite dose‐dependent effects of Alamandine and Ang II on the Na+/H+ exchanger may represent an important physiological regulation in terms of intra‐ and extracellular volume and/or pH changes.Support or Funding InformationFAPESP; CNPq and CAPESThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.