Renin in the human kidney

Summary We have localized the enzyme renin (EC 3.4.99.19) in the normal adult human kidney by immunohistology. Serial paraffin sections of kidneys were incubated with renin antisera and then processed by the peroxidase-antiperoxidase method. Renin immunoreactivity was observed in the juxta-glomerular epithelioid granular cells (JEG-cells) in the wall of the afferent and rarely of the efferent vessel of the glomerulus. JEG-cells have long cytoplasmic processes penetrating between adjacent cells. This suggests a possible paracrine release of renin. Staining of various segments of the tubular system was shown to be artifactual. The kidney proteins recognized by our anti-human renin antisera had similar characteristics to renin when determined by a combination of gel-electrophoretic and immunologic techniques. Renin immunostaining in the juxtaglomerular apparatus of the human kidney is discrete and reflects the low amount of extractable renin.Dedicated to Prof. G. Töndury on the occasion of his 75th birthday     

Angiotensin II in epitheloid (Renin containing) cells of rat kidney

Summary The PAP-method was used for immunocytochemical investigations with antisera against angiotensin (ang) I, ang II and renin in kidneys of rats and mice. In 14 rats, ang II was found in the media of the afferent arteriole — both in the region of the JGA and upstream until the interlobular artery. Serial sections alternately reacted for ang II and renin revealed that the octapeptide is contained in the well known renin positive epitheloid cells of the afferent arteriole and, beyond that, together with renin probably in the same specific granules. Fixation conditions were critical for the visualization of immunoreactivity. With ang I antisera, comparable in terms of titer and affinity to the ang II antisera, specific immunoreactivity could not be found in the kidneys of rats. With horse radish peroxidase and ferritin as tracers it could be shown that the epitheloid cells of the JGA have the ability to pinocytize and incorporate macromolecules into their granules. It is suggested that ang II is taken up by these cells through the same route. Intracellular generation of ang II appears unlikely as an explanation. Functionally the selective uptake of ang II by epitheloid cells might be a specific process, possibly connected with the negative feedback of the octapeptide on renin secretion. Negative results in mice may be explained by a small uptake or more rapid degradation of ang II by the epitheloid cells.These studies were supported by the Deutsche Forschungsgemeinschaft within the SFB 90 Cardiovasculäres System. A first brief report of the results was given at the Rottach-Egern Satellite Symposium of the VIIth International Congress on Nephrology: The Juxtaglomerular Apparatus and the Tubulo-Glomerular Feedback Mechanism — Morphology, Biochemistry and Function, June 3 to 5, 1981     

Renin expression in the kidney and brain is reciprocally controlled by captopril

The tissue distribution of rat renin mRNA was examined. Sensitive RNase protection analyses demonstrated that renin mRNA are produced by the extra-renal tissues such as adrenal, brain, liver, lung, pituitary and testis. In response to sodium depletion and captopril treatment, the expression of mRNAs encoding rat renin were in a tissue-specific manner. The level of kidney renin mRNA remarkably increased in sodium-depleted rats treated with captopril, whereas that of brain renin mRNA definitely decreased. No significant change in the level of liver renin mRNA was observed after the same treatment. These results suggest that the expression of cerebral renin is regulated by physiological stimuli independent of its extra-cerebral expression.     

Role of prostaglandis in the control of renin secretion in the dog (II)

Infusion of prostaglandin E₁ (PGE₁) into the renal artery of anesthetized dogs (1.03 μg/min) caused increases in urine flow rate (V), renal plasma flow (RPF) and renin secretion rate without any change in mean arterial blood pressure (MABP), whereas infusion of prostaglandin F₂α (PGF_2α), (1.03 μg/min) caused no consistent change in V, RPF, or renin secretion rate. Infusion of prostaglandin E₂ (PGE₂) (1.03 μg/min) into the renal artery of “non-filtering” kidneys caused renin secretion rate to rise from 567.7 ± 152.0 U/min(M ± SEM) during control periods to 1373.6 ± 358.5 U/min after 60 minutes of infusion of PGE₂ (P < 0.01), without significant change in MABP (P > 0.1). The data suggest that PGE₁ and PGE₂ play a role in the control of renin secretion. The data further suggest that PGE may control renin secretion through a direct effect on renin-secreting granular cells.     

Effect of ergocristine on prolactin secretion in the male rat with pituitaries grafted beneath the kidney capsule.

Male rats in which three pituitaries were grafted beneath the kidney capsule showed approximately a fourfold increase in circulating plasma prolactin concentration. The elevated plasma prolactin concentration did not remain at a constant level but fluctuated with time. The elevated prolactin concentration declined immediately after a single bolus injection of ergocristine (30 micrograms/kg). The slope of the prolactin decay curve, determined by sequential blood sampling, was parallel to a theoretical slope having a 7-min half-life. This result indicates that ergocristine blocked prolactin secretion immediately and completely as the decay curve (T 1/2 = 6.5 min, confidence interval 4.5--11.3) resulting from the administration of ergocristine is the same as the endogenous prolactin decay curve (T 1/2 = 7 min).     

Para-aminohippuric acid secretion by the vertebrate kidney

Tubular secretory capacity has been investigated in the kidney of marine fishes Scorpaena porcus, Spicara smaris, frog Rana ridibunda and albino rat by determination of maximal transport of p-aminohippurate--TmPAH, Following values of Tmax expressed in mg/hour per 100 g of body weight were obtained: 0.73 +/- 0.17 for S. porcus, 0.92 +/- 0.09 for S. smaris, 0.93 +/- 0.10 for R. ridibunda and 15.6 +/- 1.6 for rats.     

Electrogenic bicarbonate secretion by prairie dog gallbladder

Pathological rates of gallbladder salt and water transport may promote the formation of cholesterol gallstones. Because prairie dogs are widely used as a model of this event, we characterized gallbladder ion transport in animals fed control chow by using electrophysiology, ion substitution, pharmacology, isotopic fluxes, impedance analysis, and molecular biology. In contrast to the electroneutral properties of rabbit and Necturus gallbladders, prairie dog gallbladders generated significant short-circuit current (I(sc); 171 +/- 21 microA/cm(2)) and lumen-negative potential difference (-10.1 +/- 1.2 mV) under basal conditions. Unidirectional radioisotopic fluxes demonstrated electroneutral NaCl absorption, whereas the residual net ion flux corresponded to I(sc). In response to 2 microM forskolin, I(sc) exceeded 270 microA/cm(2), and impedance estimates of the apical membrane resistance decreased from 200 Omega.cm(2) to 13 Omega.cm(2). The forskolin-induced I(sc) was dependent on extracellular HCO(3)(-) and was blocked by serosal 4,4'-dinitrostilben-2,2'-disulfonic acid (DNDS) and acetazolamide, whereas serosal bumetanide and Cl(-) ion substitution had little effect. Serosal trans-6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl-chroman and Ba(2+) reduced I(sc), consistent with the inhibition of cAMP-dependent K(+) channels. Immunoprecipitation and confocal microscopy localized cystic fibrosis transmembrane conductance regulator protein (CFTR) to the apical membrane and subapical vesicles. Consistent with serosal DNDS sensitivity, pancreatic sodium-bicarbonate cotransporter protein pNBC1 expression was localized to the basolateral membrane. We conclude that prairie dog gallbladders secrete bicarbonate through cAMP-dependent apical CFTR anion channels. Basolateral HCO(3)(-) entry is mediated by DNDS-sensitive pNBC1, and the driving force for apical anion secretion is provided by K(+) channel activation.     

Renin substrate in granules from rat kidney cortex.

1. Subcellular fractions of rat kidney cortex generated angiotensin I continuously over 2h when incubated at 37degreesC with rat renin, indicating the presence of renin substrate within cells in the renal cortex. 2. Renin substrate was located in highest specific concentration in particulate fractions. The particles containing renin substrate had a sedimentation velocity slightly lower than mitochondria and renin granules but greater than the microsomal fraction. 3. Isopycnic gradient centrifugation indicated a density of 1.190g/ml for the particles containing renin substrate, compared with 1.201 for renin granules, 1.177 for mitochondria, and 1.170 and 1.230 for lysosomes in the heavy-granule fraction. 4. In the liver, renin substrate was also found in particles, but these had a lower sedimentation rate than those from the kidney. 5. The molecular weights of renin substrate in kidney and liver granules and rat plasma were similar, namely 61000-62000. 6. On the basis of these biochemical findings, a mechanism for the intrarenal production of angiotensin, incorporating a subcellular reaction scheme, is proposed.     

Gonadotroph-rich cell lines derived from pituitary clonal cells (2A8) grafted under the kidney capsule

Summary Gonadotroph-rich cell lines were established from multipotential pituitary clonal cells (2A8) which were implanted under kidney capsule of hypophysectomized female rats. These cell lines secrete gonadotrophins (FSH and LH) continuously over two months after establishment; LHRH stimulated the secretion of hormones into the culture medium. Many of the cells reacted immunohistochemically to antiserum to FSH or LH, while a small number reacted to antiserum to prolactin or TSH. They did not contain normal secretory granules such as those of gonadotrophs in vivo.Supported by USPHS Grant HD 11826 and NIH Grant P30 HD 10202. The authors wish to thank James Chambers (Immunocytochemistry), and Pat Koym and John Rhode (Radioimmunoassay) for their excellent technical assistance. We also express our thanks to NIAMDD for providing pituitary hormones