Magnesium (Mg2+) is an important cofactor in many intracellular bioche
mical reactions; however, its role in the signal transduction pathways
of pulmonary vascular smooth muscle is poorly defined, The purpose of
this study was to examine the following mechanisms of pulmonary vascu
lar smooth relaxation in the presence and in the absence of Mg2+: (1)
Endothelium-dependent cGMP-mediated relaxation (response to acetylchol
ine, ACh), (2) Endothelium-independent cGMP-mediated relaxation (respo
nse to sodium nitroprusside, SNP), and (3) beta(2)-adrenergic cAMP-med
iated relaxation (response to isoproterenol, ISO). Dose response curve
s were generated in isolated rat pulmonary artery rings preconstricted
with phenylephrine. With Mg2+, ACh 10(-6) M produced complete ring re
laxation but in the absence of Mg2+, only 66% relaxation was produced
in response to ACh 10(-6) M (P < 0.05). On the other hand, endothelium
-independent cGMP-mediated relaxation (response SNP) was not impaired
without Mg2+. beta(2)-adrenergic cAMP-mediated relaxation was also imp
aired in the absence of Mg2+. In the presence of Mg2+, ISO 10(-6) M pr
oduced complete relaxation but without Mg2+, only 30% relaxation was p
roduced (P < 0.05). We conclude that Mg2+ is essential for cGMP- and c
AMP-mediated mechanisms of pulmonary vasorelaxation. Hypomagnesemia sh
ould be avoided to prevent pulmonary vasomotor dysfunction. (C) 1996 A
cademic Press, Inc.