Juxtaglomerular Granular Cells Research Articles

Effect of low-level renal nerve stimulation on renin release from nonfiltering kidneys.

The mechanism whereby renal nerves influence the renin-release response to aortic constriction was examined in a nonfiltering ureter-occluded kidney preparation in anesthetized dogs. The kidney was rendered nonfiltering by a combination of mannitol infusion and ureteral occlusion. Suprarenal aortic constriction reduced renal perfusion pressure to 61 +/- 7 mmHg and increased renin release from 16.7 +/- 4.1 to 26.1 +/- 6.0 U/min. At normal renal perfusion pressure, low-frequency renal nerve stimulation (0.25 Hz) increased renin release by 11.6 +/- 4.2 to 25.1 +/- 7.6 U/min. The effect of combined low-level renal nerve stimulation and aortic constriction on renin release was additive; renin release increased by 24.6 +/- 6.5 to 39.5 +/- 7.3 U/min. Propranolol or metoprolol, administered intrarenally at 2 microgram . min-1 . kg-1, abolished the renin-release response to low-level renal nerve stimulation at normal renal perfusion pressure. These data provide evidence that low-frequency renal nerve stimulation influences the renin-release response to reduction in renal perfusion pressure in a nonfiltering ureter-occluded kidney with an inoperative macula densa receptor mechanism. The neural effect on renin release at normal renal perfusion pressure is mediated via beta 1-adrenoceptors probably located on the juxtaglomerular granular cells.

Angiotensin II immunoreactivity coexists with renin in the juxtaglomerular granular cells of the kidney.

The multiple physiologic functions of angiotensin II(AII) are generally supposed to be mediated by the peptide generated in the blood circulation. In addition to this extracellular mechanism of AII formation, we have obtained immunohistochemical evidence for the intracellular synthesis of AII in the kidney. Rats were perfused with fixative, and paraffin sections of the kidneys were processed with antisera against renin (EC 3.4.99.19), AII, and other components of the renin--angiotensin system. Renin immunoreactivity was regularly observed in the epithelioid granular cells in the media of the afferent vessel of the glomerulus. AII immunoreactivity was found to coexist within the same cells. This observation points to an intracellular production of AII in the juxtaglomerular epitheloid granular cells. AII may then be released concomitantly with renin in the interstitial fluid and in the blood. The paracrine secretion of AII could exert a local regulatory influence on the tonus of the glomerular vessels.

Localization of tritiated norepinephrine in the renal arteriolar nerves.

The innervation of the glomerular arterioles was investigated by light and electron microscopy autoradiography for localization of exogenous tritiated norepinephrine. By light microscopy accumulations of grains were seen associated with afferent arterioles and in lesser numbers with efferent arterioles and neighboring tubules. Accumulations of grains were noted to be in contact with juxtaglomerular granular cells. Electron microscopy autoradiography revealed that nearly two-thirds of the silver grains were on axons. Most of the label was on varicosities packed with small, clear and dense-cored, vesicles. Most varicosities, including those in contact with smooth muscle, juxtaglomerular granular or tubular cells, were labeled. Some varicosities which appeared unlabeled in a given section were labeled in subsequent sections. These findings are consistent with the notion that the glomerular arterioles are innervated mainly by adrenergic nerves. This view is supported by the previously reported observations of the concomitant virtual disappearance of fluorescent and acetylcholinesterase-positive nerves from the region of the glomerular arterioles after two injections of six-hydroxydoapmine (a drug which selectively destroys adrenergic nerves) and the presence of small dense-cored vesicles in all axons of the juxtaglomerular region when examined by serial section electron microscopy.

Anatomy of the juxtaglomerular apparatus

The juxtaglomerular apparatus, located in the glomerular hilum, consists of a vascular component (afferent and efferent arterioles and extraglomerular mesangium) and a tubular component (macula densa). Two types of contact between vascular and tubular components are observed: a) a complex type, involving distal tubule, extraglomerular mesangium, and proximal efferent arteriole, and b) a simple type, consisting of apposition of the basement membranes of the vascular and tubular components. Juxtaglomerular granular cells, the source of renin, are present throughout the vascular component but are more numerous in the afferent arteriole. They can be considered as "myoendocrine" cells, since they contain myofibrils and attachment bodies, together with secretory granules and crystalline protogranules. Macula densa cells differ from those elsewhere in the distal tubule in that their nuclei are closer to each other, the Golgi apparatus is basally located, and their basal membrane infoldings are less prominent. Adrenergic nerves are demonstrable by fluorescence histochemistry in the juxtaglomerular region. Electron microscopy reveals unmyelinated nerve fibers containing small dense-cored vesicles and capable, as shown by ultrastructural autoradiography, of incorporating exogenous tritiated norepinephrine. Neuroeffector junctions occur between nerves and cells of the vascular and, less frequently, the tubular component. In addition, adrenergic axons are observed in a juxtaglomerular cell tumor. Nerve terminals are seen in direct contact with the tumor cells.

Stretch receptor control of renin release in perfused rat kidney: effect of high perfusate potassium.

1. These studies were conducted in the isolated perfused rat kidney to determine the effect of high perfusate K on the renin release induced by low perfusion pressure, renal vasoconstriction and isoprenaline, and to determine whether the magnitude of the K-induced inhibition equalled that observed with renal vasodilation and high perfusion pressure. 2. Raising perfusate K concentration from 4.2 to 56 mM suppressed basal renin release, and the 56 mM-K inhibited the renin release induced by low perfusion pressure (50 mmHg) or phenylephrine (0.83 micrometers). 3. Isoprenaline (0.79 micrometers) induced a marked increase in renin release; but high perfusate K, propranolol (0.28 mM), papaverine (0.39 mM), or high perfusion pressure (150 mmHg) inhibited this effect. 4. It is concluded that high perfusate K has a powerful inhibitory effect on the renin release induced by renal hypotension, vasoconstriction, and isoprenaline infusion, and that this effect may be mimicked by high perfusion pressure or renal vasodilation. A mechanism is proposed whereby these signals may inhibit renin release by depolarizing the juxtaglomerular granular cells.

Juxtaglomerular granular cells and nephron autoregulation

AbstractHistological study of serially sectioned glomeruli in rat and mouse kidneys possessing different aggregates of juxtaglomerular granular cells has revealed that between 15 and 29% of glomeruli in control animals are not associated with these granular cells and that almost universal association occurs only when the granular cells are greatly increased. Thus, a significant number of nephrons in control rats are not continuously autoregulated through a local renin‐angiotensin mechanism, assuming that a lack of granules is associated with a lack of synthesis and release of renin. This association between granular cells and glomeruli is usually greater in the outer half than in the inner half of the cortex regardless of the content of granular cells; although the difference is not as great as prior reports indicate. Stimuli which either increase or decrease granularity of juxtaglomerular cells produce a similar and parallel response in both cortical regions, suggesting that control or regulation of granular cells is the same in both areas. It further suggests that the reported difference in filtration rates between superficial and deep glomeruli following sodium loading and sodium deprivation is not mediated through a differential alteration of juxta‐glomerular cell granularity. A linear regression equation was developed by which the per cent of all glomeruli associated with granular cells may be estimated from given mean juxtaglomerular granular cell indices (GCI).

BASIC FUCHSIN-CRYSTAL VIOLET; A RAPID STAINING SEQUENCE FOR JUXTAGLOMERULAR GRANULAR CELLS EMBEDDED IN EPOXY RESIN.

A basic fuchsin-crystal violet staining sequence for demonstration of juxtaglomerular granular cells in epoxy-embedded tissues is rapid and results in slides with excellent contrast and intensity. Procedure: Cut sections 0.3-0.6 μ thick. Hydrate through xylene and alcohol to water. Stain in modified Goodpasture's stain (basic fuchsin, 1; aniline, 1; phenol, 1; 30% alcohol, 100) for 20-30 sec; rinse in tap water; stain in modified Stirling's (crystal violet, 5; alcohol, 10; aniline, 2; water, 88) for 20-30 sec; rinse in tap water and dry on a hotplate; mount in a synthetic resin. Granular cells of the juxtaglomerular apparatus are stained an intense dark blue by the crystal violet. Arterial elastic membranes and collagen are pale blue. Other structures are shades of red.

ELECTROLYTE AND JUXTAGLOMERULAR CHANGES IN ADRENAL REGENERATION HYPERTENSION.

One week after adrenal enucleation in rats skeletal muscle and serum electrolytes followed a pattern similar to adrenal insufficiency. However, at the 2nd week of adrenal regeneration there was a marked shift of sodium into and potassium out of skeletal muscle cells which persisted through the 8th week. These cation shifts correlated with increases in blood pressure and renal and heart weights. Increased sodium and decreased potassium in skeletal muscle cells and increased blood pressure and increased renal and heart weights were potentiated by saline feeding and failed to occur with adrenal regeneration in the hepatic portal circulation. Juxtaglomerular granular cells were examined in rats killed at 1, 2, 4, 6, and 8 weeks after adrenal enucleation. No evidence was found to indicate a change which would be expected to initiate a blood pressure rise and the degranulation observed was interpreted as the result rather than the cause of the blood pressure change.

Effect of Adrenal Enucleation and of the Spironolactone SC-8109 on Granularity of Rat Juxtaglomerular Cells1

The granular cell index, a measure of the incidence of juxtaglomerular granular cells, was determined at intervals of from 3 hr to 22 days after uninephrectomy, uniadrenalectomy and enucleation of the remaining adrenal in weanling rats drinking 1 % saline. The index during this period exhibited a biphasic pattern characterized by an initial transitory elevation followed by a sustained reduction. The non-antihypertensive spironolactone, SC-8109, prevented the reduction phase without blocking adrenal regeneration. Cortisone prevented the depression phase but it also blocked adrenal regeneration. Water and electrolyte levels of serum and skeletal muscle were not correlated with changes in the index. In the complete absence of adrenal tissue, sustained reduction of the index could be produced only with DOC and not with cortisone or saline. The data show that reduction of the granular cell index which occurs during adrenal regeneration is adrenal-dependent. It is suggested that this reduction, although not cau...