Abnormal magnesium metabolism in etiology of salt-sensitive hypertension and type 2 diabetes mellitus.
A previously unknown genetic defect in magnesium metabolism (i.e., the magnesium-binding defect [MgBD]) was found to be associated with the cause of "salt-sensitive" essential hypertension in humans and rats. It inhibits the entrance of Mg2+ into the cell so that the intracellular concentrations of Mg2+ and MgATP2- are decreased. Consequently, the 300 enzyme reactions in the cell, especially the 100 that either use or produce MgATP2-, are inhibited. Thus, because the extrusion of intracellular Na+ requires MgATP2-, hypertension results when the involved MgATP2- requiring enzyme is inhibited. The MgBD is corrected by the tachykinin substance P, which occurs in normal blood plasma, and by the pentapeptide and its contained tetrapeptide, which are released from the C-terminal region of substance P by plasma aminopeptidases. In vivo, the intravenous administration of the tetrapeptide corrects the hypertension and the MgBD as well. The MgBD also occurs in type 2 diabetes mellitus and, thus, the decreased intracellular concentrations of Mg2+ and MgATP2- ions appear to be involved also in the cause of this disease, which is reputed to be the fifth most deadly disease in the world.
Wells
Ibert C
IC
Department of Medicine, Creighton University School of Medicine, Omaha, NE 68178, USA.
Agrawal
Devendra K
DK
Anderson
Robert J
RJ
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D051381:Rats; D020303:Rats, Inbred Dahl; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D015320:Tachykinins / Q000627:therapeutic use
D015320:Tachykinins; D000255:Adenosine Triphosphate; D012964:Sodium; D008274:Magnesium