Coexisting independent sodium-sensitive and sodium-insensitive mechanisms of genetic hypertension in spontaneously hypertensive rats (SHR)

Abstract

Some essential hypertensive patients and genetic hypertensive rat strains have less than the normal levels of Mg2+ tightly bound to the plasma membranes of their erythrocytes and other cells, i.e., the magnesium binding defect (MgBD). This binding defect appears to cause increased passive permeability of the membrane to Na+ and thereby its increased intracellular concentration, particularly if the Na+-extrusion enzyme systems of the cell are also defective. The Na+-Ca2+ exchange system in the cell membrane exports Na+ and imports Ca2+, increasing the tone of the smooth muscle cell and thus producing hypertension (HTn). This HTn is Na+-sensitive. Evidence supporting this postulate was obtained by determining the intraerythrocyte total concentrations of Na+, Ca2+, K+, and Mg2+ in two strains of spontaneously hypertensive rats (SHR and SS/Jr rats, having the MgBD together with the other requisites of the Na+-sensitive pathway) and their respective controls (WKY and SR/Jr rats, in which this complete pathway is absent). The Na+ and Ca2+ concentrations in the hypertensive rats were increased, and that of K+ was decreased. The concentrations of these cations were very similar in the two hypertensive strains. The level of membrane tightly bound Ca2+ in SHR erythrocyte membranes was significantly higher than those in the other three rat strains, which were not statistically different from each other. These results support previously reported evidence of the existence of a novel HTn-generating mechanism in the SHR rat, in which the intracellular Ca2+ concentration is increased as the result of the enhanced diffusion of this ion into the cell and the accompanying deficiency of the Ca2+ extrusion enzyme systems. This pathway is therefore Na+-insensitive, i.e., Ca2+-sensitive.

Evidence that the etiology of the syndrome containing type 2 diabetes mellitus results from abnormal magnesium metabolism

“…Further, the intracellular magnesium ion concentration in these studies correlated significantly and inversely with the average blood pressure of the subjects involved. This result suggested a possible causal relationship, which was later confirmed (Wells and Blotcky 2001), between the decreased intracellular concentration of magnesium ions and Na + -sensitive essential hypertension.…”

Sodium–Calcium Exchanger in Pulmonary Artery Smooth Muscle Cells

“…[23][24][25][26][27] Consistent with the established importance of NCX1 in systemic vascular SMCs, a number of studies have shown that the hypertension is associated with changes in the activity of NCX in various types of arterial beds. [28][29][30][31][32][33][34] Using the specific inhibitor of Ca 2+ entry through NCX1 SEA0400, NCX1-deficient mice, and transgenic mice that specifically express NCX1.3 in smooth muscle, Iwamoto et al have recently demonstrated that salt-sensitive hypertension is triggered by Ca 2+ entry through NCX1 in arterial smooth muscle. 35 Pulmonary circulation is structurally and functionally different from systemic circulation at the regional tissue, cellular, and molecular levels.…”

Na + /Ca 2+ Exchanger

“…5,6 Dysregulation of [Ca 2ϩ ] i can lead or contribute to deleterious pathogenic conditions, including neurodegenerative diseases 7 and salt-sensitive hypertension. 1,8 Recently, there has also been a preponderance of evidence implicating oxidative stress in the pathogenesis of hypertension, 9,10 and this effect of oxidative stress might occur, at least in part, through alterations in [Ca 2ϩ ] i dynamics. Because the NCX is 1 of the primary regulators of [Ca 2ϩ ] i , alterations in [Ca 2ϩ ] i dynamics under oxidative stress conditions might be attributed, at least to some extent, to dysregulation of the NCX.…”