(Hypertension. 1999;34:442-449.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Activation of the Na+-H+ Exchanger Modulates Angiotensin II–Stimulated Na+-Dependent Mg2+ Transport in Vascular Smooth Muscle Cells in Genetic Hypertension
From the Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
Correspondence to R.M. Touyz, MD, PhD, Clinical Research Institute of Montreal, 110 Pine Ave W, Montreal, Quebec, H2W1R7 Canada. E-mail touyzr{at}ircm.qc.ca
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
pHi/s) compared with WKY (0.05±0.004
pHi/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.
Key Words: Na+ • pH • signal transduction • vascular resistance • vasoconstriction • magnesium • rats, SHR
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