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

Touyz, R.M. and Schiffrin, E.L. (1999) Activation of the Na+-H+ exchanger modulates angiotensin II stimulated Na+-dependent Mg2+ transport in vascular smooth muscle cells in genetic hypertension. Hypertension, 34(3), pp. 442-449. (doi: 10.1161/01.HYP.34.3.442)

Abstract

This study investigated the role of the Na+-H+ exchanger (NHE) on angiotensin II (Ang II)–induced activation of Na+-dependent Mg2+ transport in vascular smooth muscle cells (VSMCs) from Wistar-Kyoto rats (WKY; n=20) and spontaneously hypertensive rats (SHR; n=20). Intracellular free concentrations of Mg2+ ([Mg2+]i) and Na+ ([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 Mg2+ 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 [Mg2+]i was lower in SHR than WKY (0.59±0.01 versus 0.71±0.01 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 [Mg2+]i. Responses were significantly greater (P<0.05) in SHR versus WKY ([Na+]i Emax=37.5±1.1 versus 33.7±1.9 mmol/L; pHi Emax=7.35±0.04 versus 7.20±0.01; [Mg2+]i Emin=0.28±0.09 versus 0.53±0.02 mmol/L, SHR versus WKY). In Na+-free buffer, Ang II–elicited [Mg2+]i responses were inhibited. MIA (1 μmol/L) inhibited Ang II–stimulated responses in WKY and normalized responses in SHR ([Mg2+]i Emin=0.49±0.02). Ang II–stimulated activation of NHE was significantly increased (P<0.05) in SHR (0.07±0.002 ΔpHi/s) compared with WKY (0.05±0.004 ΔpHi/s). These data demonstrate that in VSMCs [Mg2+]i regulation is Na+ dependent, that activation of NHE modulates Na+-Mg2+ transport, and that increased activity of NHE may play a role in altered Na+-dependent regulation of [Mg2+]i in SHR.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Touyz, Professor Rhian
• Authors: Touyz, R.M., and Schiffrin, E.L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Hypertension
• Publisher: American Heart Association
• ISSN: 0194-911X
• ISSN (Online): 1524-4563