Renin-positive granulated Goormaghtigh cells. Immunohistochemical and electron-microscopic studies on biopsies from patients with pseudo-Bartter syndrome.

It is difficult to distinguish between Goormaghtigh cells (G-cells) and media cells of the glomerular arterioles at the border of the Goormaghtigh cell field. Consequently, it has been unclear whether renin-positive G-cells are normally present and also whether renin-producing cells are recruited from the pool of renin-negative G-cells upon stimulation of the renin-angiotensin system (RAS). In the present study, immunohistochemical and electron-microscopic experiments have been carried out on serially sectioned kidney biopsies from four patients with pseudo-Bartter syndrome.

Hypothetical interpretation of the calcium paradox in renin secretion.

Most renin-positive cells of the preglomerular arteriole are intermediate in morphological appearence between smooth muscle cells and epithelioid cells. Intermediate cells contain, in addition to secretory granules, contractile proteins arranged as a sublemmal network. The paradoxical (inhibitory) role of calcium in renin secretion is explained, on the basis of these findings, by an increased tone of the sublemmal network; this might impair the preexocytotic access of renin granules to the cell membrane.

Morphology of electrophysiologically identified baroreceptor afferents and second order neurones in the brainstem of the cat.

Baroreceptor afferent fibres and second order baroreceptor neurones were identified by their discharge pattern and were intracellularly injected with horseradish peroxidase. Three afferent fibres and three second order neurones were reconstructed by camera lucida drawings from serial sections of the brainstem. The afferent fibres were classified as A delta-fibres and had terminal arborizations with synaptic boutons in the dorsomedial region of the nuclei of the solitary tract (TS).

Macroautophagic phenomena in renin granules.

The secretory granules of murine epithelioid cells take up and probably degrade mitochondria; they thus appear to have macroautophagic properties. As renin granules also have other properties uncommon for secretory granules, they are suggested to fulfill functions in these cells otherwise reserved for lysosomes.

Cytoplasmic sequestration phenomena in smooth muscle cells of kidney resistance vessels and epithelioid cells of the juxtaglomerular apparatus.

The occurrence of vacuoles in cells of contractile tissues and especially in media cells of resistance vessels has been known for quite some time. Recently, it has been widely accepted that these vacuoles, characteristically lined by a double membrane, result from herniation of one vascular smooth muscle cell into the other as a result of vasoconstriction. In our electronmicroscopic investigations we found double membrane-bounded vacuoles not only in kidney resistance vessels of rats and mice under conditions of vasoconstriction, but also in control animals and animals with maximal renal vasodilation.

The juxtaglomerular apparatus in Bartter's syndrome and related tubulopathies. An immunocytochemical and electron microscopic study.

A comparative immunocytochemical and electron microscopic study was performed on renal biopsies from two children with classical Bartter's syndrome (BS) and three children with a recently described variant, the so-called hyperprostaglandin E-syndrome (HES). Compared to age-matched controls, kidney specimens from patients with BS and HES disclosed a marked hypertrophy and hyperplasia of the juxtaglomerular apparatus (JGA). In addition, in HES focal tubular and interstitial calcifications accompanied by interstitial fibrosis and tubular atrophy were noted.

Interzonal and intrazonal heterogeneities in the renin status of the preglomerular arterioles in five species.

In five species (mouse, rat, rabbit, rhesus monkey and man) the renin status of the preglomerular arterioles was examined using two immunohistochemical methods: the measurement of the renin-positive portion of the vessels, reflecting the respective number of granulated cells, and the semiquantitative assessment of the renin concentration in the juxtaglomerular epithelioid cells with antibody dilution series. The main objective of the study was to compare the interzonal with the intrazonal internephron heterogeneities, i.e.

Tachyphylaxis of juxtaglomerular epithelioid cells to angiotensin II. Differences between the electrical membrane response and renin secretion.

A study has been made of desensitization of the depolarizing response to angiotensin II of juxtaglomerular epithelioid and vascular smooth muscle cells in the mouse kidney afferent arteriole, of media cells from the mesenteric artery as well as of cultured smooth muscle and mesangial cells. In all cell types, desensitization to this effect of angiotensin II was observed. There was no cross-desensitization between angiotensin II and other depolarizing agonists.

Effects of extracellular osmolality on renin release and on the ultrastructure of the juxtaglomerular epithelioid cell granules.

Superfusion with hypoosmotic solutions stimulates renin release from rat epithelioid cells adherent to isolated glomeruli. This stimulatory effect may be related to the observed swelling of the secretory granules; the swelling may markedly increase the probability of pre-exocytotic fusions between the granule and cell membranes, and consequently increase the frequency of exocytotic events.

The granular epithelioid cells in the kidney of the lemon sole (Pleuronectes microcephalus Donovani).

Serial sections from kidneys of 5 aglomerular lemon soles (Pleuronectes microcephalus) demonstrated the presence of anastomosing arteriolar networks in the caudal half of the organs. There was no preferred location of the networks, which were found both near the surface and in the deeper parts of the kidney. The size of the networks varied; the largest measured more than 900 micrometers in the longest axis and covered an area larger than 500,000 micrometers2, whereas the smallest measured about 60 micrometers in diameter with an area of 2040 micrometers2.

Myosin content and vasoconstrictive ability of the proximal and distal (renin-positive) segments of the preglomerular arteriole.

The PAP-technique and antibodies to myosin were used to demonstrate the prerequisites for vasoconstriction in the juxtaglomerular part of the preglomerular arteriole as compared with its proximal segment in rats and mice. In contrast with the myosin-positive/renin-negative proximal part of the afferent arteriole no myosin-like activity could be demonstrated in its distal, renin-positive part. In accordance, no thick myofilaments were found in fully differentiated juxtaglomerular epithelioid cells replete with mature secretory granules.

Intrarenal generation of angiotensin II evaluated by an electrophysiological technique.

Angiotensin II (ANG II) reversibly depolarizes renin-containing juxtaglomerular epithelioid cells (JGECs) of the hydronephrotic mouse kidney afferent arteriole. This depolarizing response was utilized to assess changes in ANG II concentration in the vicinity of JGECs in order to test whether ANG II is generated from ANG I and artificial renin substrate (ARS) in this preparation. Depolarizations were also produced by the application of ANG I and ARS in the superfusing medium.

The fate of prorenin during granulopoiesis in epithelioid cells. Immunocytochemical experiments with antisera against renin and different portions of the renin prosegment.

Comparative immunocytochemical experiments with antisera directed against renin and three synthetical peptides (Pro 1, Pro 2A and Pro 3) covering almost the entire span of human renin prosegment were performed on human kidney tissue. With anti-Pro 1, i.e.

Typical and atypical aspects of renin secretion from juxtaglomerular epithelioid cells.

A survey is given about features of renin synthesis and secretion from juxtaglomerular epithelioid cells that are largely atypical as compared to those of other secretory systems. Renin-producing cells have the capability of reversible metaplastic transformation into vascular smooth muscle cells, their secretory granules are very closely related to lysosomes, and they react paradoxically, i.e.

Atrial natriuretic peptide inhibits renin release from juxtaglomerular cells by a cGMP-mediated process.

We have examined the effect of a synthetic analogue of human alpha-atrial natriuretic peptide (ANP), APII, on renin release in cultured renal juxtaglomerular cells (JGA cells). Using cell cultures containing 80-90% renal juxtaglomerular cells, we found that ANP (10(-13)-10(-9) M) strongly inhibited renin release from the cells in a dose-dependent fashion (ki, 10 pM) to about 10% of control. Inhibition of renin release by ANP was paralleled by an increase in cellular cGMP levels; while in the presence of the cGMP-phosphodiesterase inhibitor M&B 22948 (1 mM), concentrations of ANP lower by a factor of 100 were required to obtain the same effects on renin release and cGMP levels.

Junctional transmission in renin-containing and smooth muscle cells of the afferent arteriole.

Intracellular recordings were done in renin-containing juxtaglomerular (JG) and vascular smooth muscle (VSM) cells of the mouse kidney afferent arteriole. Both cell types exhibited a membrane potential around -75 mV and spontaneous depolarizing transients resembling spontaneous excitatory junction potentials (SEJPs) in the arterioles of other organs. The amplitude distribution of these randomly occurring transients was skewed in both cell types with a modal value of 1.

Epithelioid cells: membrane potential changes induced by substances influencing renin secretion.

Microelectrode recordings were performed in renin-containing epithelioid (JG) and vascular smooth muscle (VSM) cells of the afferent arteriole in the isolated hydronephrotic mouse kidney. Both cell types had a membrane potential of about -75 mV and exhibited small, spontaneous depolarizing transients, probably resulting from random transmitter release by sympathetic axon terminals. Substances depressing renin secretion, such as angiotensin II, arginine-vasopressin, and alpha 1-adrenergic agents reversibly depolarized both JG and VSM cells.

The hydronephrotic kidney of the mouse as a tool for intravital microscopy and in vitro electrophysiological studies of renin-containing cells.

Experimental hydronephrosis in mice has been studied with histological, ultrastructural, immunohistochemical, biochemical, and electrophysiological techniques to establish its value as a preparation for the investigation of glomerular microcirculation as well as the electrophysiological and biochemical properties of the renin-containing juxtaglomerular (JG) and vascular smooth muscle (VSM) cells of the afferent glomerular arteriole. During developing hydronephrosis the kidney parenchyma becomes progressively thinner as a result of tubular atrophy, being, after 12 weeks, a tissue sheet of about 200 micron in thickness. In this preparation, the renal arterial tree, in particular the glomerular arterioles, and also the glomeruli can be easily visualized.

Role of protein kinase C in inhibition of renin release caused by vasoconstrictors.

It was the aim of the present study to get insight into some of the intracellular mechanisms by which the vasoconstrictor hormones angiotensin II (ANG II), arginine vasopressin (AVP), and norepinephrine (NE) inhibit renin release from renal juxtaglomerular cells. To this end a primary cell culture from rat renal cortex was established that consisted of 50% juxtaglomerular cells. The cultured juxtaglomerular cells contained prominent renin granules closely resembling those in the intact kidney and responded to a number of stimuli of renin release.

The morphological basis of fluid balance in the interstitium of the juxtaglomerular apparatus.

The morphological basis of fluid balance in the interstitium of the juxtaglomerular apparatus (JGA) was reevaluated in rats, mice and Tupaia. Three ultrastructural features in the region of the vascular pole of the renal corpuscle are described that may be important for the fluid balance in this region: (1) podocyte foot processes in the parietal layer of Bowman's capsule, (2) endothelial fenestrations in the wall of the incoming afferent arteriole, both facing Goormaghtigh and epithelioid cells, and (3) the mesangial-type lining of the glomerular stalk. With respect to the relevant pressure gradients, this morphology may provide the basis of bulk-fluid flow directed to the interstitium of the JGA including the Goormaghtigh cell field.

Development and fate of the secretory granules of juxtaglomerular epithelioid cells.

The development and fate of the secretory granules in murine, rat and human juxtaglomerular epithelioid cells were examined using ultrastructural and immunocytochemical methods. The formation of mature renin granules occurs by fusion of rhomboid protogranules followed by coalescence of their paracrystalline contents, and by the fusion of roundish juvenile granules having an amorphous internum. Protogranules with paracrystalline contents are prominent in animals with stimulated renin synthesis, indicating an overcharge in processing and/or packaging of the secretory product, renin, under these conditions.