Development of vascular renin expression in the kidney critically depends on the cyclic AMP pathway

Abstract

During metanephric kidney development, renin expression in the renal vasculature begins in larger vessels, shifting to smaller vessels and finally remaining restricted to the terminal portions of afferent arterioles at the entrance into the glomerular capillary network. The mechanisms determining the successive expression of renin along the vascular axis of the kidney are not well understood. Since the cAMP signaling cascade plays a central role in the regulation of both renin secretion and synthesis in the adult kidney, it seemed feasible that this pathway might also be critical for renin expression during kidney development. In the present study we determined the spatiotemporal development of renin expression and the development of the preglomerular arterial tree in mouse kidneys with renin cell-specific deletion of G(s)alpha, a core element for receptor activation of adenylyl cyclases. We found that in the absence of the G(s)alpha protein, renin expression was largely absent in the kidneys at any developmental stage, accompanied by alterations in the development of the preglomerular arterial tree. These data indicate that the maintenance of renin expression following a specific spatiotemporal pattern along the preglomerular vasculature critically depends on the availability of G(s)alpha. We infer from our data that the cAMP signaling pathway is not only critical for the regulation of renin synthesis and secretion in the mature kidney but that it also is critical for establishing the juxtaglomerular expression site of renin during development.

Fig. 1.

Renin (red) and α-smooth muscle actin (α-SMA; green) immunoreactivity in kidney sections of wild-type (WT) mice and mice with renin-expressing cell (RC)-specific deletion of G_sα (G_sα^−/−) at days 16 and 18 of embryonic development (E16 and E18), 1 day after birth (PP1), and after maturation (adult). Scale bar, 20 μm.

Fig. 2.

Reconstruction of α-SMA-immunoreactive vascular structures (red) and renin-immunoreactive areas (green) in developing kidneys of WT and RC G_sα^−/− mice as a whole organ model (A–D) and in single developing arcuate arteries (E–H) of E16 RC G_sα^−/−(A and E), E16 WT (B and F), E18 RC G_sα^−/− (C and G), and E18 WT mice (D and H). The light green color indicates glomeruli. Scale bar, 100 μm.

Fig. 3.

Length of afferent arterioles in kidneys of RC G_sα^−/− and WT mice at E16 and E18, at PP1, and after maturation (adult). Data are means ± SE of 50 afferent arterioles from both genotypes at each developmental stage; n.s., no significant difference. *P < 0.05.

Fig. 4.

Reconstruction of α-SMA-immunoreactive vascular structures (red) and renin-immunoreactive areas (green) in developing kidneys of WT and RC G_sα^−/− mice as whole organ model (A–C) and in single arcuate arteries (D–F) of PP1 RC G_sα^−/− (A and D), PP1 WT (B and E), adult RC G_sα^−/− (C), and adult WT mice (F). The light green color indicates glomeruli. Scale bar, 100 μm.