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Biomedical subjects

O Skøtt

Publications and source records attributed to O Skøtt.

At least 19 recordsLinked to original sources
PubMed1992

Lack of effect of intraluminal pressure on renin release from isolated afferent arterioles.

To evaluate the role of the proposed baroreceptor mechanism in the afferent arteriole in regulating renin release, we modified the isolated perfused tubule technique to perfuse afferent arterioles. Arterioles with attached glomeruli were isolated from rabbit kidneys and perfused using standard methods. To stop the arteriolar flow and allow perfusion pressure, as set by a mercury manometer, to be built up in the lumen of the vessel, the glomerulus was sucked into a constriction pipette. The preparation was continuously superfused with Krebs-Ringer solution in the first series of experiment, and a cell culture medium in the second series of experiment. The superfusate droplets were collected under mineral oil with 10-min collection intervals. The renin content of the samples was assayed by radioimmunoassay of the angiotensin I generated. In the two series of experiments we tested the effects of sequential changes in intraluminal pressure on renin release. In the first series of experiments (n = 6) the renin release was 56.3 nGU arteriole-1 min-1 in the first 10 min of sampling. The renin release was then constant for 80 min with an average of 21.6 nGU arteriole-1 min-1. In the last 30 min the renin release was 96.5 nGU arteriole-1 min-1. In the second series of experiments (n = 8) the renin release was 26.5 nGU arteriole-1 min-1 throughout the course of the experiment. These results indicate that under these conditions there is no relation between renin release and intraluminal pressure in afferent arterioles.

Animals↗
PubMed1992

Involvement of chloride in renin secretion from isolated rat glomeruli.

The sensitivity of renin release to changes in anion and calcium concentrations was assessed in superfused rat glomeruli with attached juxtaglomerular cells. Isosmotic substitution of Cl-with gluconate (1/12, 1/6, 1/3, 2/3, or total exchange), isethionate (15 or 101 mM), or sulfate (10 mM) inhibited renin release reversibly. Substitution of Cl- with nitrate (101 mM) stimulated renin secretion. Substitution with iodide (15 or 101 mM) had no consistent effect. The stimulation induced by calcium-free solutions was high in May and low in September. In the absence of chloride, the response to calcium-free solution was inhibited similarly all year. In May reintroduction of calcium and chloride stimulated renin release, suggesting that releasable renin had been stockpiled during the exposure to calcium-free solution. In September reintroduction of calcium and chloride inhibited renin release. It is concluded that the renin secretory process has a demand for permeant anions. The stimulation caused by low external calcium involves at least two mechanisms: one is anion sensitive, powerful, varies with the season, and includes a recruitment phenomenon; another is anion insensitive and weak.

Animals↗
PubMed1991

[Cellular and intrarenal aspects of renin secretion].

Renin is synthesized, stored and excreted from cells (JG cells) localized in the afferent glomerular arteriole. Preprorenin is formed first by biosynthesis. After splitting off of the pre-fraction, glycosylering and passage through the Golgi apparatus, prorenin, which is biologically inactive, may be excreted immediately or be stored in secretory granules where activation occurs by splitting off of the pro-fraction. Excretion of the secretory granules is regulated and takes place by exocytosis. Important intracellular signal molecules include, inter alii, calcium which is inhibitory and cyclic AMP which stimulates release. In addition, osmotic water movements also play an important role. The physiological regulatory mechanisms include 1) a baroreceptor: lowered perfusion pressure to the kidney stimulates release of renin, 2) a tubular signal: decrease in Cl(-)-concentration at the macula densa stimulates release of renin, 3) the nerve supply of the kidney which stimulates directly via beta-receptors on the JG cells and also indirectly via alpha-adrenergic influence on haemodynamic and tubular resorption and 4) local and circulating hormones, particularly angiotensin II and prostaglandins.

Calcium↗
PubMed1991

Lithium absorption by the rabbit gall-bladder.

Lithium (Li+) absorption across the low-resistance epithelium of the rabbit gall-bladder was studied in order to elucidate possible routes and mechanisms of Li+ transfer. Li+ at a concentration of 0.4 mM in both mucosal and serosal media did not affect isosmotic mucosa-to-serosa fluid absorption. At this low concentration net mucosa-to-serosa Li+ absorption was insignificant when the ambient Na+ concentration was 115 mM, although the gall-bladder had a significant Li+ permeability (2.7 X 10(-5) cm s-1) and a significant mucosa-to-serosa Li+ gradient developed as a result of fluid absorption. Net Li+ absorption was induced at reduced mucosal Na+ concentrations (by lowering the Na+ concentration down to 50 mM with or without substitution with sucrose, or by adding sucrose to the mucosal medium). This Li+ absorption occurred even in the absence of a mucosa-to-serosa Li+ gradient. Na+ and Li+ absorptions occurring at 50 mM Na+ were inhibited to the same degree by mucosal 1 mM amiloride. Substitution of 5-50 mM (44%) Na+ by Li+ in the external medium dose-dependently depressed Na+ absorption by up to 76%, while substitution by 50 mM choline had no significant effect. Li+ inhibition of Na+ absorption was elicited from the mucosal side and was not accounted for by compensatory Li+ absorption; water and Na+ absorption rates decreased nearly in parallel. The effects of 0.4 mM amiloride and of substitution with 20 mM Li+ were only partly additive. It is concluded that Li+ absorption in the rabbit gall-bladder cannot be explained by passive (paracellular) transport, but must be the result of transcellular, active transport. Both at low and at high concentrations Li+ may enter the cell via an Na+/H+ exchanger in the apical cell membrane. At high concentrations Li+ may inhibit Na+ absorption by interference with the exchange mechanism and/or via effects at the cytoplasmic level. The Li+ transfer mechanism across the basolateral cell membrane remains unknown.

Amiloride↗
PubMed1991

Renin release from isolated juxtaglomerular apparatus depends on macula densa chloride transport.

Transport inhibitor and ion substitution studies were performed using perfused, superfused preparations of the isolated rabbit juxtaglomerular apparatus to investigate transport dependency of macula densa-mediated renin secretion. In the first experimental series, tubular perfusion with a high-NaCl solution containing 10(-6) M bumetanide increased renin secretion compared with perfusion with high NaCl alone from 8.7 to 24.6 nano-Goldblatt hog units (nGU)/min. Bath addition of 10(-6) M bumetanide had no effect on renin release. The second series tested ability of luminal addition of 54 mmol/l Na or Cl salts to inhibit renin secretion, starting from a stimulated value produced by low-NaCl perfusion. Perfusion with a high-NaCl solution decreased renin secretion from 58.9 to 14.8 nGU/min, which served as a positive control. Addition of choline chloride decreased renin secretion from 42.7 to 16.6 nGU/min, and RbCl decreased renin secretion from 54.9 to 17.0 nGU/min. In contrast, addition of two different Na salts had no effect on renin release (from 41.7 to 31.6 nGU/min with sodium isethionate and from 14.1 to 13.5 nGU/min with sodium acetate). Also, in the presence of 26 mmol/l Cl, addition of 54 mmol/l Na had no effect on renin secretion (29.9-36.8 nGU/min). These data demonstrate that renin secretion is directly stimulated by luminal application of transport blockers and can be inhibited by increases in Cl concentration at the macula densa but not by changes in Na concentration. These results support the hypothesis that the initiating signal for macula densa control of renin secretion is an inverse change in transport rate via the luminal Na(+)-K(+)-2Cl- cotransporter.

Animals↗
PubMed1991

Dynamics of intrarenal pressures and glomerular filtration rate after acetazolamide.

The dynamics of intrarenal pressures, early distal tubular fluid conductivity (EDC), and renal flood flow (RBF) were studied in rats given acetazolamide (ACZ), an inhibitor of proximal reabsorption. Glomerular filtration rate (GFR) and end-proximal flow were estimated by clearances of 51Cr-EDTA and lithium. Proximal tubular pressure (Pprox) increased initially by 1.7 +/- 0.1 mmHg after ACZ, causing a decrease in the hydrostatic pressure difference across the glomerular membrane (delta P). EDC increased, and then RBF, glomerular capillary pressure (Pgc), Pprox, and star vessel pressures (Psv) dropped as a result of afferent vasoconstriction. Pprox decreased less than Pgc, resulting in a further decrease in delta P, which after 25-30 s reached a constant level 3-4 mmHg below control. After a transient increase the pressures declined to a new steady state, in which Pprox was equal to control, Pgc was decreased, and distal tubular pressure, end-proximal flow, and EDC were increased. GFR was depressed by 29%. The results indicate that the tubuloglomerular feedback mechanism controls Pgc and Pprox by afferent vasoconstriction, as well as efferent vasodilation. The data also indicate that proximal reabsorption rate is important in determining the changes in delta P by its effect on Pprox at least in the early transient phase.

Acetazolamide↗
PubMed1991

Mechanisms of renin release from juxtaglomerular cells.

In microdissected, nonperfused afferent arterioles changes in intravascular pressure did not affect renin secretion. On the contrary, renin release from isolated afferent arterioles perfused in a free-flow system has been reported to be sensitive to simultaneous changes in luminal pressure and flow. Hence local blood flow may be involved in the baroreceptor control of renin release. If flow is sensed, the sensor is likely to be located near the endothelial cell layer, where ion channels have been shown to be influenced by variations in shear stress.

Animals↗
PubMed1990

Cellular mechanisms within the juxtaglomerular apparatus.

The tubular-vascular connection via the juxtaglomerular apparatus appears to serve two functions, local control of renal vascular resistance and regulation of renin secretion. A fall in single nephron glomerular filtration rate (SNGFR) and an increase in resistance are produced by an increase in NaCl concentration at the macular densa. This change also results in inhibition of secretion of renin. The macula densa has a unique location near the terminal end of the thick ascending limb, where NaCl concentration is highly flow dependent. The cellular mechanisms by which changes in tubular fluid NaCl produce vasoconstriction and inhibition of renin secretion are unknown, but the anatomy of the juxtaglomerular apparatus strongly suggests that such responses may be mediated by the extraglomerular mesangial cells located in the polar cushion underlying the macula densa. Recent evidence suggests that interstitial chloride concentration in this compartment may be quite variable, and that increases in external chloride may enhance the activation of the mesangial cell.

Feedback↗
PubMed1990

Characterization of the macula densa stimulus for renin secretion.

These studies utilize the isolated perfused rabbit juxtaglomerular apparatus (JGA) to study the macula densa signal for renin secretion in the absence of the confounding influences of intravascular pressure and renal nerve activity. In the first experimental series, JGAs were perfused alternately with high- and low-NaCl solutions to determine the reversibility of the renin response to changes in NaCl concentration. Compared with high-NaCl controls, perfusion with a low-NaCl solution resulted in a fivefold increase in renin secretion rate (RSR) [2.1-10.0 nano-Goldblatt hog units (nGU)/min], and this response was largely reversible. When the solutions were presented in the reverse order, a similar inhibition by high NaCl was observed. In the second series, JGAs were perfused with high-, medium-, and low-NaCl solutions to determine the sensitive range of the renin response to NaCl concentration changes. The full renin response (3.2-16.6 nGU/min), similar in magnitude to that seen in series 1, was found to occur between 80 and 24 mM for Na+ and 61 and 7 mM for Cl-. In the third series, the NaCl concentration and flow rate of the perfusate were altered independently to separate the effects of flow rate, NaCl delivery, and NaCl concentration on RSR. Although a decrease in perfusate flow rate slightly increased RSR (3.4-8.1 nGU/min), a comparable decrease in NaCl concentration resulted in a much higher RSR (26.3 nGU/min). We conclude that in this preparation 1) RSR responds equally to both increases and decreases in macula densa NaCl concentration, and these changes are rapid and largely reversible, 2) the full renin response occurs within the concentration range normally occurring at the macula densa, i.e., below 80 mM Na+ and 61 mM Cl-, and 3) RSR responds with a larger change to alterations in NaCl concentration than in NaCl delivery or fluid flow rate.

Animals↗
PubMed1990

Effect of adenosine1-receptor blockade on renin release from rabbit isolated perfused juxtaglomerular apparatus.

Adenosine has been proposed to act within the juxtaglomerular apparatus (JGA) as a mediator of the inhibition of renin secretion produced by a high NaCl concentration at the macula densa. To test this hypothesis, we studied the effects of the adenosine1 (A1)-receptor blocker 8-cyclopentyl-1,3-dipropylxanthine (CPX) on renin release from single isolated rabbit JGAs with macula densa perfused. The A1-receptor agonist, N6-cyclohexyladenosine (CHA), applied in the bathing solution at 10(-7) M, was found to inhibit renin secretion, an effect that was completely blocked by adding CPX (10(-5) M) to the bath. Applied to the lumen, 10(-5) M CPX produced a modest stimulation of renin secretion rates suppressed by a high NaCl concentration at the macula densa (P less than 0.05). The effect of changing luminal NaCl concentration on renin secretion rate was examined in the presence of CPX (10(-7) and 10(-5) M) in the bathing solution and in vehicle control experiments. The control response to increasing luminal NaCl concentration was a marked suppression of renin secretion, that was maintained as long as luminal NaCl concentration was high and was promptly reversible when concentration was lowered. CPX did not alter renin release when luminal NaCl was low, but diminished the reduction caused by high NaCl (P less than 0.01). It is concluded that A1-receptors are located within the JGA, and that A1-receptor activation inhibits renin release. A high NaCl concentration at the macula densa appears to influence A1-receptor activation, but a low NaCl concentration does not. The findings support participation of adenosine in macula densa control of renin secretion.

Adenosine↗
PubMed1989

Influence of bicarbonate on the sensitivity of renin release to sodium chloride.

Juxtaglomerular cells in vitro are sensitive to changes in osmolality, but it is unknown whether volume-regulatory changes in cellular ion fluxes are important for the renin secretory process. The sensitivity of renin release to increases in osmolality by NaCl was therefore tested on superfused rat glomeruli treated with bicarbonate/chloride exchange inhibitor (DNDS), NaCl/KCl cotransport inhibitor (bumetanide), or Na+/H+ antiport inhibitor (amiloride) in the presence or absence of bicarbonate. In addition, the sensitivity to increases in osmolality by addition of sucrose was tested in the presence or absence of bicarbonate. Renin release from time controls superfused with a bicarbonate-free Ringer was identical to release from glomeruli superfused with a bicarbonate Ringer. DNDS (0.11 or 1.1 mM) had no effect on renin release in a bicarbonate Ringer. 30 mM sucrose inhibited renin release independently of bicarbonate. 15 mM NaCl stimulated renin release when bicarbonate was absent, while it caused an inhibition in the presence of bicarbonate. When bicarbonate/chloride exchange was inhibited, addition of NaCl stimulated renin release even when bicarbonate was present. The effect of NaCl on renin release was not affected by amiloride (1 mM) or bumetanide (10 microM). Thus, volume regulatory mechanisms as known from other cells are not involved in the renin secretory response to small increases in NaCl concentration. Furthermore, the sensitivity of renin release to changes in NaCl concentrations is modulated by bicarbonate in a way that depends on a functioning anion-exchange mechanism. The results are compatible with the existence in the membrane of the secretory granule of a Cl-/HCO3- exchange mechanism which mediates exit of Cl-, and thereby attenuates granular swelling and exocytotic release.

Animals↗
PubMed1989

Studies on renin release in vitro.

1) Measurements of renin secretion from single arterioles at time intervals down to 20 seconds showed that the renin secretion is episodic, the amount of renin released during each episode corresponding to the estimated content of one secretory granule. 2) A decrease in osmolality elicits episodic release of renin from single arterioles, stimulates renin release from isolated glomeruli transiently, and is associated with swelling of the secretory granules and formation of contacts between granules and the plasmalemma. 3) Increases in osmolality produce sustained inhibition of the renin secretion, and prevents swelling of the organelles of the juxtaglomerular epithelioid cells. 4) Treatment of isolated glomeruli with weak permeable bases has a biphasic effect on renin release: an initial transient stimulation, which can be blocked with sucrose, and a delayed inhibition which may be associated with an increase in intracellular pH. 5) Results with the monovalent cation ionophores nigericin and monensin, are similar to those obtained with weak permeable bases, and suggest that their effects are due to swelling and alkalinization of acidic cellular organelles. 6) A decrease in the extracellular calcium concentration results in sustained stimulation of renin secretion to a variable level dependent on the season. 7) After stimulation with a low extracellular calcium concentration, the sensitivity of secretion rate to osmotic stimuli is proportionally increased. A high extracellular osmolality blocks the stimulatory effect of a low calcium concentration. 8) Renin release is not correlated to the release of adenylate kinase.

Animals↗
PubMed1988

Effects of osmolality and calcium on renin release from superfused rat glomeruli treated with nigericin or monensin.

Proton gradients may be important for the induction of swelling and exocytosis of secretory renin granules during basal renin release (RR). The sensitivity of renin release to changes in osmolality and to calcium was therefore tested on superfused rat glomeruli that had been pretreated with the monovalent cation/proton ionophores monensin and nigericin to dissipate granular proton gradients. Furthermore it was tested whether NH4Cl stimulates RR by inducing waterfluxes. Pretreatment of glomeruli with 10 microM nigericin or monensin inhibited RR, and suppressed the response to calcium removal, independently of the presence of 0.5 mM EGTA. In contrast, the stimulatory effect of a hypo-osmotic challenge (-20 mM sucrose) was unchanged after pretreatment with nigericin or monensin. The stimulation induced by 15 mM NH4Cl was prevented by addition of 20 mM sucrose. The results suggest that dissipation of proton gradients with the ionophores inhibit RR late in the secretory pathways, independently of effects on the Golgi-apparatus and intracellular calcium concentration. The results are consistent with the hypothesis that a low granular pH is important for driving JGC-granule swelling and exocytosis.

Ammonium Chloride↗