Background: 

Gap junctions composed of connexins coordinate microcirculatory vascular function. Cx45 is expressed in vascular smooth muscle (VSM) but its function is unclear. Thus, we studied expression and function of Cx45 using different mouse models allowing to identify and delete Cx45.

Methods: 

VSM-directed deletion was achieved by the Cre-lox system using Cre-recombinase driven by a Nestin promoter. Deletion of Cx45 leads to the expression of enhanced green fluorescence protein (eGFP) in these mice. The conduction of vasomotor responses was studied in arterioles of the cremaster muscle using intravital microscopy and blood pressure was measured by telemetry.

Results: 

Cx45 expression in VSM was detected by immunohistochemistry in wildtype arterioles, by eGFP expression in VSM-directed Cx45-deficient mice (Cx45fl/fl:Nestin-Cre) as well as by detection of eGFP at VSM cell borders in arterioles of mice expressing an eGFP-tagged Cx45 fusion protein. As expected, arteriolar conduction of endothelium-dependent acetylcholine-induced dilations was not different in Cx45fl/fl:Nestin-Cre mice from control mice harbouring homozygously floxed Cx45 coding DNA (Cx45fl/fl). Surprisingly, the amplitude of locally induced endothelium-independent constrictions (K⁺) and dilations (adenosine) declined similarly with distance in both genotypes. Mean arterial pressure was not different between awake Cx45fl/fl and Cx45fl/fl:Nestin-Cre mice (101±7 vs. 114±4 mmHg, n=5 each, P=0.13).

Conclusion: 

Cx45 is expressed in VSM of murine arterioles under physiological conditions. However, Cx45 is dispensable for the conduction of vasomotor responses along these arterioles. Possibly, other connexin isoforms (e.g. Cx43) can functionally compensate for the lack of Cx45 in VSM. Its reported role in renin secretion does not seem to alter arterial pressure in awake mice.