Connexins 40 and 43 are differentially regulated within the kidneys of rats with renovascular hypertension

Background. Connexin 40 (Cx40) is a gap junction protein expressed in endot helial cells of vessels, endocardium. and conducting cells of the His-Purki nje system of heart. Its distribution in the kidney remains to be fully inv estigated. Methods. To address this distribution. we generated rabbit antibodies direc ted to a polypeptide comprising amino acids 231 to 330 of the carboxy-termi nal domain of rodent Cx40, which specifically recognizes this protein at ga p junctions. Results. Immunolabeling. and in situ hybridization of kidney sections showe d that Cx40 and its transcript were coexpressed by most endothelial cells o f vessels and glomeruli, as well as by renin-secreting cells. This distribu tion contrasted with that of Cx43. which was expressed in some tubules of m edulla and sparse endothelial cells. Cx40 and Cx43 expression were investig ated further in a renin-dependent model of hypertension, in which rats show ed an increase in arterial mean blood pressure four weeks after clipping on e renal artery [two kidney, one-clip (2K1C) model]. Northern blot analysis of polyA(+) RNA demonstrated that, compared with sham-operated animals, the hypertensive 2K1C animals featured an increase in Cx40 mRNA expression in both left (clipped) and right (unclipped) kidneys. In contrast. Cx43 mRNA e xpression was only increased in the latter organ. Antibodies confirmed that the levels of Cx40 were actually increased in the kidneys of hypertensive animals (Western blots) and this was caused, at least in part, by enhanced expression of this protein in the renin-secreting cells of the afferent art eriole (immunofluorescence). Conclusions. Cell-to-cell communication mediated by Cx40 may be implicated in the function of renin-secreting cells, hence participating in the contro l of blood pressure.