Activation of the Na-H Exchanger Modulates Angiotensin II–Stimulated Na-Dependent Mg Transport in Vascular Smooth Muscle Cells in Genetic Hypertension

This study investigated the role of the Na-H exchanger (NHE) on angiotensin II (Ang II)–induced activation of Na-dependent Mg transport in vascular smooth muscle cells (VSMCs) from Wistar-Kyoto rats (WKY; n520) and spontaneously hypertensive rats (SHR; n520). Intracellular free concentrations of Mg ([Mg]i) and Na 1 ([Na]i) and intracellular pH (pHi) were measured with the specific fluorescent probes mag–fura 2-AM, SBFI-AM, and BCECF-AM, respectively. Na dependency of Mg transport was assessed in Na-free buffer, and the role of the NHE was determined with the highly selective NHE blocker 5-(N-methyl-N-isobutyl) amiloride (MIA). Basal [Mg]i was lower in SHR than WKY (0.5960.01 versus 0.7160.01 mmol/L, P,0.05). Basal pHi and [Na ]i were not different between the 2 groups. Ang II dose dependently increased [Na]i and pHi and decreased [Mg ]i. Responses were significantly greater (P,0.05) in SHR versus WKY ([Na]i Emax537.561.1 versus 33.761.9 mmol/L; pHi Emax57.3560.04 versus 7.2060.01; [Mg]i Emin50.2860.09 versus 0.5360.02 mmol/L, SHR versus WKY). In Na -free buffer, Ang II–elicited [Mg]i responses were inhibited. MIA (1 mmol/L) inhibited Ang II–stimulated responses in WKY and normalized responses in SHR ([Mg]i Emin50.4960.02). Ang II–stimulated activation of NHE was significantly increased (P,0.05) in SHR (0.0760.002 DpHi/s) compared with WKY (0.0560.004 DpHi/s). These data demonstrate that in VSMCs [Mg]i regulation is Na 1 dependent, that activation of NHE modulates Na-Mg transport, and that increased activity of NHE may play a role in altered Na-dependent regulation of [Mg]i in SHR. (Hypertension. 1999;34:442-449.)