Salt-Sensitive Hypertension in Transgenic Mice Overexpressing Na ⁺ -Proton Exchanger

Abstract

Essential hypertension is one of the most common diseases that exacerbate the risk of cardiovascular or cerebrovascular attacks. Although the etiology of essential hypertension remains unclear, recent investigations have revealed that an enhancement of Na(+)-proton (Na(+)-H+) exchange activity is a frequently observed ion transport abnormality in hypertensive patients and animal models. To test the hypothesis that increased Na(+)-H+ exchange causes hypertension, we produced transgenic mice overexpressing Na(+)-H+ exchanger and analyzed their Na+ metabolism and blood pressure. Urinary excretion of water and Na+ was significantly decreased in transgenic mice, and systolic blood pressure was elevated after salt loading. The impaired urinary excretion of Na+ suggested that the Na(+)-H+ exchanger overexpressed in the renal tubules increased reabsorption of Na+, which caused a blood pressure elevation by Na+ retention after excessive salt intake. Our results demonstrate that overexpression of Na(+)-H+ exchanger can be a genetic factor that interacts with excessive salt intake and causes salt-sensitive blood pressure elevation.

G-395A polymorphism in the promoter region of the KLOTHO gene and hypertension among elderly (90 years and older) Chinese individuals

“…Discovered by Kuro-o et al (1995) during the development of hypertensive transgenic mice models, the KLOTHO gene, a new anti-aging gene (Wang and Sun, 2009), has recently attracted considerable attention from researchers around the world (Kuro-o, 2009). The identification of SNPs in the human KLOTHO gene is currently one of the most active areas of research.…”

Endothelial Dysfunction and Blood Pressure Variability in Selected Inbred Mouse Strains

“…[1][2][3][4][5][6] Transgenic mouse models of hypertension have also been developed through the overexpression of genes such as the sodium hydrogen exchanger or, from our own laboratory, the human renin and human angiotensinogen genes. 7,8 Although these mouse models have proven useful to better understand some of the underlying mechanisms of hypertension and vascular disease, it is important to be aware that the genetic background of the mice used to generate these models may influence the observed phenotype. As an example, Schlager and Weibust, 9 using the tail-cuff method, observed a wide range of blood pressure among 15 different inbred mouse strains.…”

The 825C/T Polymorphism of the G-Protein Subunit β3 Is Not Related to Hypertension

“…Different investigators have demonstrated enhanced NHE isoform-1 (NHE-1) activity in several blood cell lines of patients with essential hypertension compared with normotensive control subjects, 1,2 and transgenic mice that overexpress a recombinant NHE protein developed salt-sensitive hypertension. 3 Siffert et al 4 have demonstrated that immortalized B lymphoblasts of patients with essential hypertension, which display enhanced NHE-1 activity, also showed increased activity of pertussis toxin-sensitive G proteins. Variations in NHE-1 transcripts could not be detected, 5 and polymorphisms in genes that encode the subunits of trimeric G proteins, such as G␣ i2 , G␣ i3 , G␤ 1 , and G␤ 2 , 6 have been ruled out.…”