A Role of Intestine in Hypertension: Mechanism of Suppression of Intestinal Na-H Exchanger Isoform-3 in Spontaneously Hypertensive Rats

Abstract

The main objective of this study was to investigate the role and the underlying mechanism of Na-H exchanger-3 (NHE-3) expression in spontaneously hypertensive rat (SHR) intestine. Expression of colonic and ileal NHE-3 isoform, its regulatory factor-1 (NHERF-1) and cyclic GMP kinase II (cGKII) were examined using western blot analysis. Since NHE-3 activity is regulated by its abundance on the plasma membrane, its levels were also examined in lipid rafts-enriched membrane fractions. The lipid rafts fractions were characterized by examining the concentration of flotillin-1 and caveolin-1, total protein, and cholesterol. Twelve-weeks-old SHR used in this study developed significant hypertension, proteinuria, and renal and cardiac hypertrophy. These changes were significantly reversed by captopril treatment. There was a significant decrease in the levels of NHE-3 and NHERF-1 proteins, and sodium pump activity, but an increase in the cGKII levels in both tissues from SHR. Reduction in NHERF-1 levels was reversed by captopril but not of the other proteins. Cholesterol profile was significantly different in SHR colon as compared to normo-tensive Wistar Kyoto rats. These findings suggest that suppression of NHE-3 in intestine is a counteracting mechanism of hypertension and is regulated by NHERF-1 through cGKII activation in SHR. NHE-3 suppression together with decrease in the sodium pump activity would accumulate intracellular Na⁺ and may contribute to the reported hypertension-induced tissue damage in the GI-tract.

• Na-H exchanger
• Na-K ATPase
• hypertension
• Ileum
• NHERF
• colon
• SHR

ACKNOWLEDGMENTS

The authors thank the Research Administration of Kuwait University (Grant YM 06/10), and the College of Graduate Studies, Kuwait University for their financial support.

The authors thank the Research Core Facility, Faculty of Medicine, Kuwait University for providing access to instrumentation facility.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.