Functional connexin40 protein (Cx40) is mandatory for conduction in arterioles and blood pressure control

Cx40 is a crucial component in gap junctions (GJ) with a strong impact on function. Cx40‐deficient mice exhibit hypertension, renin excess, and impaired conduction of endothelium‐dependent dilations. However, Cx37 expression is reduced in these mice which may relate to hypertension or purely to the lack of Cx40. A human mutation in Cx40 (Ala96→Ser, A96S) leads to non‐conducting GJ allowing to distinguish between these possibilities. Therefore, we studied conduction of vasomotor signals and blood pressure in mice carrying this mutation (Cx40 A96S ) in vivo. In arterioles of these mice, mutated Cx40 was identified in the endothelial cell membrane. Interestingly, Cx37 was also found in Cx40 A96S to a similar amount as in wildtype. Locally confined arteriolar stimulation by acetylcholine (ACh), bradykinin (Bk), or KCl elicited dilations which spread upstream without decline of the amplitude in wildtype. In contrast, in Cx40 A96S the amplitude declined for these dilators with increasing distance significantly. Conducted dilations initiated by adenosine declined similarly in both genotypes. Arterial pressure was increased by 23 mmHg in Cx40 A96S . In summary, a functional channel forming Cx40 is required to support conducted dilations and for renin‐dependent pressure regulation. Despite dysfunctional Cx40 and hypertension, Cx37 was located in the cell membrane which is, however, not able to sustain Cx40 function.