Activation of the Na+-H+ exchanger modulates angiotensin II-stimulated Na+-dependent Mg2+ transport in vascular smooth muscle cells in genetic hypertension

This study investigated the role of the Na+-H+ exchanger (NHE) on angiotens in II (Ang II)-induced activation of Na+-dependent Mg2+ transport in vascul ar smooth muscle cells (VSMCs) from Wistar-Kyoto rats (WKY; n=20) and spont aneously hypertensive rats (SHR; n=20). Intracellular free concentrations o f Mg2+ ([Mg2+](i)) and Na+ ([Na+](i)) and intracellular pH (pH(i)) were mea sured with the specific fluorescent probes mag-fura 2-AM, SBFI-AM, and BCEC F-AM, respectively. Na+ dependency of Mg2+ transport was assessed in Na+-fr ee buffer, and the role of the NHE was determined with the highly selective NHE blocker 5-(N-methyl-N-isobutyl) amiloride (MIA), Basal [Mg2+](i), was lower in SHR than WKY (0.59+/-0.01 versus 0.71+/-0.01 mmol/L, P<0.05). Basa l pH(i) and [Na+](i) were not different between the 2 groups. Ang II dose d ependently increased [Na+](i) and pH(i) and decreased [Mg2+](i). Responses were significantly greater (P<0.05) in SHR versus WKY ([Na+](i) E-max=37.5/-1.1 versus 33.7+/-1.9 mmol/L; pH(i) E-max=7.35+/-0.04 versus 7.20+0.01; [ Mg2+](i) E-min=0.28+/-0.09 versus 0.53+/-0.02 mmol/L, SHR versus WKY). In N a+-free buffer, Ang II-elicited [Mg2+](i) responses were inhibited. MIA (1 mu mol/L) inhibited Ang II-stimulated responses in WKY and normalized respo nses in SHR ([Mg2+](i) E-min=0.49+/-0.02). Ang II-stimulated activation of NHE was significantly increased (P<0.05) in SHR (0.07+/-0.002 Delta pH(i)/s ) compared with WKY (0.05+/-0.004 Delta pH(i)/s). These data demonstrate th at in VSMCs [Mg2+](i) regulation is Na+ dependent, that activation of NHE m odulates Na+-Mg2+ transport, and that increased activity of NHE may play a role in altered Na+-dependent regulation of [Mg2+](i) in SHR.