The localization of renin in the juxtaglomerular apparatus and The nerve supply of the renal vessels

The localization of renin in the juxtaglomerular apparatus - Tigerstedt and Bergman found that pressor activity was confined almost entirely to cortical extracts, but it could not be found in the most superficial layers which contain no glomeruli. Later, it was found that renin could be extracted from collections of glomeruli, from individual glomeruli isolated by microdissection and finally, from the vascular poles of isolated glomeruli.

Renin activity in the granular epithelioid cells was identified by immunofluorescent methods and a correlation was found between the granulation index (a method of quantifying the granulation of the epithelioid cells) and the renin content of the kidney under different experimental conditions. The source of renin was narrowed down still further by microdissection until finally Cook was able to remove granules from individual epithelioid cells and found that they contained renin.

Thurau et al. (1970) found that all the factors necessary to produce angiotensin II (i.e. renin, renin substrate and converting enzyme) are present within the kidney, renin and converting enzyme being present in the juxtaglomerular apparatus.

The nerve supply of the renal vessels

Both myelinated and unmyelinated nerves may be found in kidney. The former are probably afferent and their distribution has, until recently, been controversial since they had previously only been studied by light microscopy. Recently, however, Zimmerman (1975) has investigated their distribution in ultrathin sections and by electron microscopy.

He found myelinated nerves in the perivascular connective tissue of the larger intrarenal arteries, including the arcuate arteries, but they are greatly outnumbered by unmyelinated fibres and their distribution is restricted to the cortex.

There have been many studies of the innervation of the renal vessels with unmyelinated fibres and these have been reviewed by Dieterich (1974) in a well-documented study. Dieterich re-examined the whole rat kidney with respect to its nerve supply and confirmed many previous findings. Thus, nerve bundles were found to accompany the larger arteries and also the interlobular arteries.

They also accompany the afferent and efferent arterioles, the latter only in those segments which contain smooth muscle cells. In the outer cortical region, therefore, only a short segment of the efferent arteriole is innervated but in the juxtamedullary efferents a long stretch of the vessel is accompanied by bundles of nerve fibres and these extend through the subcortical zone to the outermost part of the outer medulla, since, as was mentioned above, smooth muscle cells are found around the proximal parts of the vasa recta.

Deeper in the outer medulla, however, where the smooth muscle cells are replaced by perivascular cells, no nerve fibres are found, nor are there any in the inner medulla.

In the juxtaglomerular apparatus, electron microscopy has shown nerve endings in relation to both the granular epithelioid cells of the afferent arteriole and the macula densa. Barajas and Muller (1973) have made a detailed electron microscopical study of the innervation of a single juxtaglomerular apparatus from the outer cortical region of a rat kidney.

They found that about half of the granular cells and one-sixth of the agranular cells of the afferent and efferent arterioles were innervated directly. Only three out of the thirty lacis cells had a nerve ending in the vicinity. Some axons innervated a number of cells of different types.

The problem of deciding whether the nerves are adrenergic or cholinergic is more difficult. Many investigators have used one of the fluorescence techniques to demonstrate adrenergic nerves and these are considered to give reliable results. Others have used histochemical techniques to demonstrate acetylcholinesterase by light microscopy and, more recently, by electron microscopy (Barajas et al. 1974).

The fluorescence techniques, in the hands of numerous investigators, have suggested that all the nerves described above are adrenergic and this is supported by the work of Barajas and Muller (1973) who found that all the nerves in the vicinity of the juxtamedullary apparatus contain dense-cored vesicles. On the other hand, many authors have described an extremely widespread network of nerves containing acetylcholinesterase and it has been suggested that many adrenergic nerve libres (not only in the kidney) do, in fact, contain this enzyme.

This has recently been confirmed by Barajas and his colleagues who examined the distribution of acetylcholinesterase in the cortex of monkey kidneys (Barajas et al. 1974). They found that the pattern of nerves giving a positive reaction corresponds exactly to that of the catecholamine-containing nerves.

Barajas and Wang (1975) then examined the nerves in the glomerular arterioles of rats, estimating the extent of innervation by a special quantitative method. It was found that the extent of innervation by nerve fibres showing fluorescence was the same as that for acetylcholinesterase containing fibres.

After treatment with 6-hydroxydopamine, which specifically destroys adrenergic nerve terminals, there was complete loss of fluorescence and reduction to less than 1 per cent of acetylcholinesterase activity. It was concluded that the lindings support the theory that acetylcholinesterase plays a role in adrenergic transmission.

Read the full article: The Anatomy of the Renal Circulation