Vascular and renal function of cGMP signalling
© Schlossmann et al; licensee BioMed Central Ltd. 2011
Published: 1 August 2011
Signalling by NO/cGMP is significant for regulation of cardiovascular and renal function.
For the functional analysis of cGMP signalling, transgenic murine mutants were used. cGKI signalling pathways include interaction of the cGKIβ-isozyme with the inositol 1,4,5-trisphosphate receptor I (IP3RI) associated protein cGMP kinase substrate (IRAG). NO/cGMP and ANP/cGMP-dependent relaxation of aortic smooth muscle was strongly affected in IRAG-deficient mice. NO/ANP-dependent inhibition of intracellular calcium release was suppressed in IRAG-deficient vascular smooth muscle cells (VSMC). Furthermore, reduction of store operated calcium entry by cGMP was affected in IRAG-KO VSMC. Basal mean arterial blood pressure, heart rate and activity were not changed in IRAG knockout mice. However, under pathophysiological conditions like sepsis (induced by E. coli lipopolysaccharide application) IRAG knockout mice were resistant to blood pressure reduction.
These results suggested that cGKI/IRAG signalling is a predominant signal transduction pathway of NO/ANP/cGMP which may be involved in vascular diseases including pathophysiological modulation of blood pressure. Further results provided evidence that cGMP signalling is essential for prevention of renal diseases suppressing interstitial fibrosis.
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.