title: 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.
authors: Department of Biochemistry, Faculty of Medicine, Kuwait University , Kuwait.
authors: Asmaa
authors: A
authors: Abu-Ghefreh
authors: Islam
authors: I
authors: Khan
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism; D003106:Colon / Q000503:physiopathology; D062967:Cyclic GMP-Dependent Protein Kinase Type II / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*; D007082:Ileum / Q000503:physiopathology; D007422:Intestines / Q000503:physiopathology*; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002352:Carrier Proteins; C495537:Cav1 protein, rat; D051242:Caveolin 1; D008565:Membrane Proteins; D010750:Phosphoproteins; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; C106354:flotillins; C093376:sodium-hydrogen exchanger regulatory factor; D002216:Captopril; D062967:Cyclic GMP-Dependent Protein Kinase Type II; D000254:Sodium-Potassium-Exchanging ATPase