Altered cellular magnesium responsiveness to hyperglycemia in hypertensivesubjects

Previous studies by our group have identified ionic aspects of insulin resi stance in hypertension, in which cellular responses to insulin were influen ced by the basal intracellular ionic environment-the lower the cytosolic fr ee magnesium (Mg-i), the less Mg-i increased following insulin stimulation. To investigate whether this ionic insulin resistance represents a more gen eral abnormality of cellular responsiveness in hypertension, we studied Mgi responses to nonhormonal signals such as hyperglycemia (15 mmol/L) and use d P-31-nuclear magnetic resonance (NMR) spectroscopy to measure Mg-i in ery throcytes from normal (NL, n= 14) and hypertensive (HTN, n= 12) subjects be fore and 30, 60, 120, and 180 minutes after in vitro glucose incubations. B asal Mg-i levels were significantly lower in HTN subjects than in NL subjec ts (169 +/- 10 versus 205 +/-8 mu mol (.) L (-1), P <0.01). In NL cells, hy perglycemia significantly lowered Mg-i, from 205 +/-8 mu mol (.) L-1 (basal , T = 0) to 181 +/-8, 162 +/-6, 152 +/-7, and 175 +/-9 mu mol (.) L-1 (T = 30, 60, 120, and 180, respectively; P <0.005 versus T=0 at all times). In H TN cells, maximal Mg-i responses to hyperglycemia were blunted, from 169 +/ - 10 mu mol (.) L-1 (basal, T=0) to 170 +/- 11, 179 +/- 12, 181 +/- 14, and 17315 mu mol (.) L-1 (T=30, 60, 120, and 180, respectively; P=NS versus T= 0 at all times). For all subjects, Mg-i responses to hyperglycemia were clo sely related to basal Mg-i levels: the higher the Mg-i, the greater the res ponse (n=26, r=0.620, P <0.001). Thus, (1) erythrocytes from hypertensive v is-a-vis normotensive subjects are resistant to the ionic effects of extrac ellular hyperglycemia on Mg-i levels, and (2) cellular ionic responses to g lucose depend oil the basal Mg-i environment. Altogether, these data suppor t a role for altered extracellular glucose levels in regulating cellular ma gnesium metabolism and also suggest the importance of ionic factors in dete rmining cellular responsiveness to nonhormonal as well as hormonal signals.