Acta Physiologica 2005; Volume 185, Supplement 649
Belgian Society for Fundamental and Clinical Physiology and Pharmacology, Autumn Meeting 2005
NO-MEDIATED VASCULAR SMOOTH MUSCLE RELAXATION IN SGCA1 KNOCK-OUT MICE
Abstract number: ORAL-3
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
Soluble guanylyl cyclase (sGC) is composed of one a and one b subunit, each existing in 2 isoforms (a1/a2 and b1/b2). The aim of our study was to investigate the functional importance of the sGCa1-subunit in several sGC-mediated vasorelaxations. Therefore, we studied blood vessels from mice lacking the sGCa1 subunit. From mice of both genders, segments of the thoracic aorta and femoral artery were mounted in a small vessel myograph for isometric tension recording. Concentration-response curves were established on acetylcholine (ACh) (1 nM10 mM), sodium nitroprusside (SNP) (1 nM10 mM), NO gas (1 mM100 mM), BAY 41-2272 (1 nM10 mM), and levcromakalim (Lev) (1 mM100 mM) in control conditions and/or in the presence of ODQ. The relaxing influence of endogenous NO (released from the endothelium in response to ACh), exogenous NO (delivered by the NO-donor SNP and NO gas) and BAY 41-2272 (an NO-independent sGC-activator) was significantly reduced in the arteries of the sGCa1 knock-out mice. However, preparations from sGCa1 knock-out mice still showed a substantial relaxation in response to exogenous NO and BAY 41-2272. The sGC-inhibitor ODQ strongly diminished the remaining effect of exogenous NO. The sGCa1 knock-out mice and their wild type littermates showed a similar response to the KATP-channel opener Lev, indicating that the reduced NO- and BAY 41-2272-induced responses are not aspecific. All observations were similar in both sexes. Taken together, these findings indicate that the sGCa1b1 isoform is involved in the vasorelaxing effect of both endogenous and exogenous NO. However, the substantial relaxation response to exogenous NO still observed in the sGCa1 knock-out mice suggests the contribution of the sGCa2b1 isoform or other ODQ sensitive mechanism.The vasorelaxing effect of BAY 41-2272 in the sGCa1 knock-out mice, indicates that both sGC isoforms are present in the blood vessels studied.
To cite this abstract, please use the following information:
Acta Physiologica 2005; Volume 185, Supplement 649 :ORAL-3