Impaired conduction of vasodilation along arterioles in connexin40-deficient mice

Connexins have been hypothesized to play an important role in intercellular communication within the vascular wall and may provide a mechanistic expla nation for conduction of vasomotor responses. To test this hypothesis, we s tudied the transmission of vasomotor responses in the intact skeletal muscl e microcirculation of connexin40-deficient mice (Cx40(-/-)). Arterioles wer e locally stimulated with hyperpolarizing dilators (acetylcholine [ACh] as well as bradykinin [Bk]) or depolarizing K+ solution, and the resulting cha nges in diameter were measured using a videomicroscopy technique at the sit e of application and up to 1.32 mm upstream. Arterial pressure was elevated 25% in Cx40(-/-) mice (94 +/- 5 versus 75 +/- 4 mm Hg). Vessels selected f or study had equivalent basal diameter and vasomotor tone in both genotypes of mice. Vasomotion was present in small arterioles of both genotypes, but its intensity was exaggerated in Cx40(-/-) mice. ACh and Bk induced dilati on (33% and 53%, respectively, of maximal response) at the site of applicat ion that was of similar magnitude in both genotypes. These dilations were o bserved to spread upstream within <1 second without significant attenuation in Cx40(+/+) mice. However, spreading was severely attenuated in Cx40(-/-) animals (11+/-4% versus 35+/-7% with ACh and 38+/-5% versus 60+/-7% with B k in Cx40(-/-) and Cx40(+/+) respectively; P<0.05). In contrast, conducted vasoconstrictions, induced by Kt solution decreased equally with distance i n both genotypes, These results support a significant role for Cx40 in vasc ular intercellular communication. Our observations indicate that Cx40 is re quired for normal transmission of endothelium-dependent vasodilator respons es and may underlie altered vasomotion patterns.