Renin: origin, secretion and synthesis

Abstract

Renin is a central hormone in the control of blood pressure and various other physiological functions. In spite of the very early discovery of renin over 100 years ago, we have only recently gained a deeper understanding of the origin of renin-producing cells and of the mechanisms responsible for renin synthesis and secretion. The main source of renin is the juxtaglomerular cells (JGCs), which release renin from storage granules. Besides the renin-angiotensin system (RAS) in the JGCs, there exist local RASs in various tissues. JGCs originate in situ within the metanephric kidney from mesenchymal cells that are not related to smooth muscle lineages, as hitherto assumed. The previous notion that JGCs stem from vascular smooth muscle cells may be explained by JGC differentiation: they acquire smooth muscle markers that are maintained throughout adulthood. It has become clear that increasing intracellular free [Ca2+] inhibits renin secretion in JGCs. In contrast, cAMP stimulates renin release. Over the last decade, numerous studies on isolated JGCs and intact animals have provided contradictory results as to whether cGMP has a stimulatory or inhibitory action on renin release. More recent results strongly suggest that the effects of cGMP on renin release from JGCs involve the degradation of cAMP, which is modulated by cGMP. Finally, it has been found that not only is the production of renin modulated by enhancing or attenuating renin transcription, but renin mRNA stability is controlled by various proteins present in renin-producing cells.

Figure 1. The lineage of the JGC

Metanephric mesenchymal cells (MC) are the origin of angioblasts, from which the endothelial cells stem. MCs are also the origin of vascular smooth muscle cells and of renin precursor cells. During ontogeny, these renin precursor cells can give rise to JGCs and to a subset of arteriolar smooth muscle cells. The smooth muscle cells originating from the renin precursors seem to be the cells capable of undergoing metaplasia to renin cells. Reproduced with permission from Sequeira Lopez et al. (2001).

Figure 2

A, immunolabelling of renin protein in a JGC using rabbit anti-mouse renin antibody, B, effects of cGMP on whole-cell currents and C_m of isolated JGCs. I-V relationships before (•) and after (▪) JGCs were dialysed with 10 μmol l⁻¹ cGMP. C, as before, but JGC were dialysed with cGMP (10 μmol l⁻¹) together with the PKA blocker Rp-cAMP (25 μmol l⁻¹). Adapted from Friis et al. (2002).