The Na+/H+ antiport, cytosolic free Ca2+, and essential hypertension: a hypothesis.
We propose that in essential hypertension higher cytosolic free Ca2+ ([Ca2+]i) is associated with hyperactivity of the Na+/H+ antiport and that augmented activity of this transport system explains at least some abnormalities in Na+ metabolism associated with this disease. In low-renin essential hypertension, a higher [Ca2+]i is present not only in vascular smooth muscle cells of resistance vessels but also in juxtaglomerular cells and renal proximal tubular epithelium. A higher [Ca2+]i in juxtaglomerular cells retards renin secretion, whereas in renal proximal tubules it is associated with increased Na+ reabsorption via the Na+/H+ antiport. Thus, hyperactivity of the Na+/H+ antiport in renal tubular epithelium may be the cause of salt (NaCl) sensitivity. Ca2+ antagonists probably exert their antihypertensive effect by reducing [Ca2+]i in both vascular smooth muscle cells and renal tubular epithelium. These agents are, therefore, particularly effective in the treatment of essential hypertension in blacks and older individuals with the low-renin form of the disease, who are known to be salt sensitive.
Aviv
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Hypertension Research Center, University of Medicine & Dentistry, Newark, New Jersey 07103-2757.
Livne
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D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D006859:Hydrogen / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D008954:Models, Biological; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism*; D012982:Sodium, Dietary / Q000494:pharmacology
D012982:Sodium, Dietary; D006859:Hydrogen; D012964:Sodium; D012083:Renin; D002118:Calcium