BACKGROUND: Connexin 40 (Cx40) is a gap junction protein expressed in endothelial cells of vessels, endocardium, and conducting cells of the His-Purkinje system of heart. Its distribution in the kidney remains to be fully investigated. METHODS: To address this distribution, we generated rabbit antibodies directed to a polypeptide comprising amino acids 231 to 330 of the carboxy-terminal domain of rodent Cx40, which specifically recognizes this protein at gap junctions. RESULTS: Immunolabeling and in situ hybridization of kidney sections showed that Cx40 and its transcript were coexpressed by most endothelial cells of vessels and glomeruli, as well as by renin-secreting cells. This distribution contrasted with that of Cx43, which was expressed in some tubules of medulla and sparse endothelial cells. Cx40 and Cx43 expression were investigated further in a renin-dependent model of hypertension, in which rats showed an increase in arterial mean blood pressure four weeks after clipping one 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 expression 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 arteriole (immunofluorescence). CONCLUSIONS: Cell-to-cell communication mediated by Cx40 may be implicated in the function of renin-secreting cells, hence participating in the control of blood pressure.