Copyright © 2007, European Society of Cardiology
Functional role of the soluble guanylyl cyclase 
1 subunit in vascular smooth muscle relaxation
aDepartment of Physiology and Physiopathology, Ghent University, Ghent, Belgium
bDepartment for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology (VIB), Ghent, Belgium
cDepartment of Molecular Biology, Ghent University, Ghent, Belgium
dCardiovascular Research Center, Massachusetts General Hospital, 149, 13th street, Charlestown, MA 02129, United States
*Corresponding author. Department of Physiology and Physiopathology, De Pintelaan 185, 9000 Ghent, Belgium. Tel.: +32 9 240 33 42; fax: +32 9 240 30 59. johan.vandevoorde{at}UGent.be
Objective Soluble guanylyl cyclase (sGC), the predominant receptor for nitric oxide (NO), exists in 2 active isoforms (
2β1 and 1β1). In vascular tissue sGC1β1 is believed to be the most important. The aim of our study was to investigate the functional importance of the sGC1-subunit in vasorelaxation.
Methods Aortic and femoral artery segments from male and/or female sGC1–/– mice and wild-type littermates were mounted in a small-vessel myograph for isometric tension recording. This was supplemented with biochemical measurements of the cGMP concentration and sGC enzyme activity.
Results The functional importance of sGC1β1 was demonstrated by the significantly decreased relaxing effects of acetylcholine (ACh), sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), NO gas, YC-1, BAY 41-2272 and T-1032 in the sGC1–/– mice of both genders. Moreover, the basal and SNP-stimulated cGMP levels and basal sGC activity were significantly lower in the sGC1–/– mice. However, the relaxing effects of NO, BAY 41-2272 and YC-1 seen in blood vessels from sGC1–/– mice indicate a role for an sGC1β1-independent mechanism. The increase in sGC activity after addition of BAY 41-2272 and the inhibition of the ACh-, SNP-, SNAP- and NO gas-induced response by the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) in the sGC1–/– mice are observations suggesting that the sGC2β1 isoform is also functionally active. However, the insignificant increase in cGMP in response to SNP and the non-upregulated sGC2 expression level in the sGC1–/– mice suggest rather the involvement of (an) sGC-independent mechanism(s).
Conclusions We conclude that sGC1β1 is involved in the vasorelaxation induced by NO-dependent and NO-independent sGC activators in both genders. However, the remaining relaxation seen in the sGC1–/– mice suggests that besides sGC1β1 also the minor isoform sGC2β1 and/or (an) sGC-independent mechanism(s) play(s) a substantial role.
KEYWORDS Arteries; Nitric oxide; Endothelial function; Second messengers; Vasoconstriction/dilatation
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