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Distinct phenotypes after cell‐specific deletion of Cx40: Loss in endothelial cells impairs conduction in arterioles and loss in renin‐producing cells elevates blood pressure
Author(s) -
Jobs Alexander,
Kurtz Armin,
Wit Cor
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.973.7
Subject(s) - bradykinin , blood pressure , vasodilation , endothelium , endocrinology , renin–angiotensin system , medicine , afferent arterioles , in vivo , endothelial stem cell , chemistry , biology , microbiology and biotechnology , in vitro , biochemistry , receptor
The gap junction protein connexin40 (Cx40) is important in cardiovascular and renal physiology as concluded from mice globally deficient for Cx40. They exhibit hypertension, renin excess, and impaired conduction of dilations along the endothelium. However, the exact contribution of endothelial Cx40 vs. Cx40 expressed in renin‐producing cells is unknown. In mice carrying a cell‐specific deletion of Cx40 in endothelial (EC) or renin‐producing cells (RPC) arteriolar responses and blood pressure were measured in vivo. Local stimulation of arterioles using ACh or bradykinin (Bk) elicited dilations that conducted rapidly without attenuation of the amplitude to upstream, remote sites (1200 μm) in mice carrying a floxed Cx40 gene (control). In contrast, remote dilations were significantly attenuated in EC‐Cx40ko (ACh by 28%, Bk by 32%) but not in RPC‐Cx40ko. However, local and remote dilations initiated by adenosine were comparable in all 3 groups of mice. Interestingly, awake EC‐Cx40ko were normotensive (EC‐Cx40ko: 115, control: 113 mmHg) whereas RPC‐Cx40ko exhibited a significantly elevated mean arterial pressure (138 mmHg) and heart weight. These data demonstrate that EC‐specific deletion of Cx40 impairs conduction of endothelium‐dependent dilations, however, per se does not increase blood pressure. Conversely, elevated pressure in RPC‐Cx40ko does not affect such signal conduction along arterioles.