Brouckaert, Peter

Buys, Emmanuel

Nimmegeers, Sofie

Sips, Patrick

Van de Voorde, Johan

English

Ghent University Academic Bibliography

FUNCTIONAL IMPORTANCE OF THE SOLUBLE GUANYLYL CYCLASE 11 ISOFORM IN VASORELAXATION Nimmegeers1 S., Sips2 P., Buys2 E., Brouckaert2 P., Van de Voorde1 J. 1Department of Physiology and Physiopathology 2Department of Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology, Ghent University, Ghent, 9000, Belgium Of the two active soluble guanylyl cyclase (sGC) isoforms (11 and21), the 11 isoform is predominantly present in vascular tissue and is therefore believed to play a dominant role in vasorelaxation. This was investigated on aortic and femoral artery segments isolated from sGC1-/- mice and their wild type littermates and by measuring of the cGMP level and sGC enzyme activity. The functional importance of sGC11 was demonstrated by a significantly reduced response to acetylcholine, sodium nitroprusside (SNP), NO-gas, YC-1 and BAY 41-2272 in arteries of sGC1-/- mice. However, those substances still had a substantial relaxing effect in these arteries, indicating that not only sGC11 is involved in vasorelaxation. The non-upregulation of the sGC2 gene and the non-significant increase in cGMP-level in response to SNP, do not support the involvement of the minor sGC21 isoform and thus rather suggest (an) sGC-independent mechanism(s). The similarity in the response to the cGMP-analogue 8-pCPT-cGMP between wild type and sGC1-/- mice, indicates that the sGC1-/- mice are not more sensitive towards cGMP. The response to the phosphodiesterase type-5 inhibitor, T-1032 was nearly abolished in the arteries of the sGC1-/- mice, indicating that in those mice there is no accumulation of basal cGMP produced by sGC21. Again those findings are against the importance of sGC21. On the other hand,the inhibition of the nitric oxide-induced relaxation and cGMP production in the sGC1-/- mice by ODQ suggest that sGC21 is functionally active. This is also suggested from the significant increase in sGC activity in the sGC1-/- mice after addition of BAY-41-2272. It is concluded that besides sGC11, also sGC21 and/or(an) sGC-independent mechanism(s) has a substantial role in nitric oxide-related vasorelaxation.  

Functional importance of the soluble guanylyl cyclase 11 Isoform in vasorelaxation

https://biblio.ugent.be/publication/1149886/file/1221524.pdf

Functional importance of the soluble guanylyl cyclase 11 Isoform in vasorelaxation

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Ghent University Academic Bibliography