L ‐NAME inhibits Mg 2+ ‐induced rat aortic relaxation in the absence of endothelium
L ‐N G ‐nitro‐arginine methyl ester ( L ‐NAME; 100 μ M ), a nitric oxide synthase (NOS) inhibitor, reversed the relaxation induced by 3 μ M acetylcholine (ACh) and 2–10 m M Mg 2+ in endothelium‐intact (+E) rat aortic rings precontracted with 1 μ M phenylephrine (PE). In PE‐precontracted endothelium‐...
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| Published in | British journal of pharmacology Vol. 128; no. 2; pp. 493 - 499 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
29.01.2009
|
| Online Access | Get full text |
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| Summary: | L
‐N
G
‐nitro‐arginine methyl ester (
L
‐NAME; 100 μ
M
), a nitric oxide synthase (NOS) inhibitor, reversed the relaxation induced by 3 μ
M
acetylcholine (ACh) and 2–10 m
M
Mg
2+
in endothelium‐intact (+E) rat aortic rings precontracted with 1 μ
M
phenylephrine (PE). In PE‐precontracted endothelium‐denuded (−E) rat aorta, 3 μ
M
ACh did not, but Mg
2+
caused relaxation which was reversed by
L
‐NAME, but not by
D
‐NAME.
The concentration response profiles of
L
‐NAME in reversing the equipotent relaxation induced by 5 m
M
Mg
2+
and 0.2 μ
M
ACh were not significantly different.
L
‐NAME (100 μ
M
) also reversed Mg
2+
‐relaxation of −E aorta pre‐contracted with 20 m
M
KCl or 10 μ
M
prostaglandin F
2α
(PGF
2α
).
L
‐N
G
‐monomethyl‐arginine (
L
‐NMMA; 100 μ
M
) was also effective in reversing the Mg
2+
‐relaxation.
Addition of 0.2 m
M
Ni
2+
, like Mg
2+
, caused relaxation of PE‐pre‐contracted −E aorta, which was subsequently reversed by 100 μ
M
L
‐NAME.
Reversal of the Mg
2+
‐relaxation by 100 μ
M
L
‐NAME in PE‐precontracted −E aorta persisted following pre‐incubation with 1 μ
M
dexamethasone or 300 μ
M
aminoguanidine (to inhibit the inducible form of NOS, iNOS).
Pretreatment of either +E or −E aortic rings with 100 μ
M
L
‐NAME caused elevation of contractile responses to Ca
2+
in the presence of 1 μ
M
PE.
Our results suggest that
L
‐NAME exerts a direct action on, as yet, unidentified vascular smooth muscle plasma membrane protein(s), thus affecting its reactivity to divalent cations leading to the reversal of relaxation. Such an effect of
L
‐NAME is unrelated to the inhibition of endothelial NOS or the inducible NOS.
British Journal of Pharmacology
(1999)
128
, 493–499; doi:
10.1038/sj.bjp.0702737 |
|---|---|
| ISSN: | 0007-1188 1476-5381 |
| DOI: | 10.1038/sj.bjp.0702737 |