Involvement of the cyclic GMP pathway in the superoxide-induced IP3 formation in vascular smooth muscle cells.
OBJECTIVE
To investigate whether cGMP or cAMP signal pathway is indirectly involved in the effect of superoxide on the IP3 formation in vascular smooth muscle cells (SMC) from rat mesenteric arteries.


METHODS
Cultured smooth muscle cells from rat mesenteric arteries were prelabelled with myo-(2-(3)H) inositol for evaluation of IP3 formation. Quantitative cAMP and cGMP levels were determined using cAMP [3H] or cGMP [125I] assay systems.


RESULTS
In the present study, it was found that superoxide significantly inhibited the basal level of cGMP and also suppressed the sodium nitroprusside (SNP)-induced cGMP formation in SMCs from rat mesenteric arteries. The inhibitory effect of superoxide on basal level of cGMP was similar in the absence or presence of ODQ (a guanylyl cyclase inhibitor). Moreover, the superoxide-induced increase in IP3 formation was significantly inhibited by SNP or s-nitroso- n-acetylpenicillamine but was significantly potentiated by ODQ or KT5823 (a cGMP-dependent protein kinase inhibitor). Superoxide had no effect on the basal or on the forskolin-induced cAMP production and the inhibition of adenylyl cyclase or cAMP-dependent protein kinase did not affect the superoxide-enhanced IP3 formation.


CONCLUSIONS
The decreased cross-inhibition of IP3 pathway by cGMP may contribute to the superoxide-enhanced IP3 formation in SMCs from mesenteric arteries. The cross-talk between cGMP and IP3 pathways provides a novel mechanism for the signalling role of superoxide in vascular SMCs.
Wu
L
L
Groupe de recherche sur le système nerveux autonome, Faculté de Médicine, Université de Montréal, Québec, Canada.
Girouard
H
H
de Champlain
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000494:pharmacology*
D013481:Superoxides; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D006152:Cyclic GMP