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

1991 ◽  
Vol 260 (4) ◽  
pp. F486-F493 ◽  
Author(s):  
J. N. Lorenz ◽  
H. Weihprecht ◽  
J. Schnermann ◽  
O. Skott ◽  
J. P. Briggs
Keyword(s):  
Chloride Transport ◽  
Choline Chloride ◽  
Juxtaglomerular Apparatus ◽  
Positive Control ◽  
Macula Densa ◽  
Renin Secretion ◽  
Renin Release ◽  
Nacl Solution ◽  
Sodium Isethionate ◽  
Ion Substitution

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.

scholarly journals Differential effects of extracellular anions on renin secretion from isolated perfused rat kidneys

1994 ◽  
Vol 267 (6) ◽  
pp. F1076-F1081 ◽  
Author(s):  
H. Scholz ◽  
K. H. Gotz ◽  
M. Hamann ◽  
A. Kurtz
Keyword(s):  
Chloride Transport ◽  
Chloride Concentration ◽  
Calcium Sensitivity ◽  
Macula Densa ◽  
Renin Secretion ◽  
Renin Release ◽  
Secretory Process ◽  
Ang Ii ◽  
Nitrate Anions ◽  
Rat Kidneys

We investigated the relevance of anions for the regulation of renin secretion from the kidneys. For this purpose we measured renin release from isolated rat kidneys that were perfused with medium containing either 120 mmol/l (normal) chloride or 95 mmol/l of isethionate, acetate, or nitrate anions in exchange for equimolar amounts of chloride. Lowering the extracellular chloride concentration by either of these maneuvers significantly enhanced renin secretion rates (RSR) at a perfusion pressure of 100 mmHg. Increasing pressure above 100 mmHg inhibited renin release in the presence of isethionate and acetate but not with nitrate anions. The renin stimulatory effects of isethionate and acetate but not that of nitrate anions disappeared in the presence of bumetanide (100 mumol/l), an inhibitor of macula densa chloride transport. Activation of renin secretion by isethionate and acetate was blunted with 100 pmol/l angiotensin II (ANG II), whereas tenfold higher concentrations of ANG II were required to attenuate the effect of nitrate ions. The amount of renin released in the presence of nitrate was fully additive to RSR values obtained with maximally effective doses of isoproterenol. These findings are consistent with the idea that impermeant anions such as isethionate and acetate enhance renin secretion from the kidneys predominantly via the tubular macula densa mechanism. The stimulatory influence of membrane-permeable nitrate anions appears to involve additional pathways and is mediated by a decreased calcium sensitivity of the renin secretory process rather than resulting from an adenosine 3',5'-cyclic monophosphate-dependent action.

Effect of prostaglandin synthesis inhibition on macula densa-stimulated renin secretion

1993 ◽  
Vol 265 (4) ◽  
pp. F578-F583 ◽  
Author(s):  
S. G. Greenberg ◽  
J. N. Lorenz ◽  
X. R. He ◽  
J. B. Schnermann ◽  
J. P. Briggs
Keyword(s):  
Direct Evidence ◽  
Juxtaglomerular Apparatus ◽  
Macula Densa ◽  
Renin Secretion ◽  
Renin Release ◽  
Cyclooxygenase Inhibitors ◽  
Flufenamic Acid ◽  
Rabbit Kidney ◽  
Nacl Concentration

The purpose of the present studies was to evaluate directly the role of prostaglandins in macula densa-mediated renin release. Individual juxtaglomerular apparatus specimens were microdissected from rabbit kidney and perfused with a solution containing either high NaCl (Na+ = 141 meq/l; Cl- = 122 meq/l) or low NaCl (Na+ = 26 meq/l; Cl- = 7 meq/l) concentration. With a step decrease in perfusate NaCl (high to low), renin secretion rate was markedly stimulated (from 15.06 to 63.1 nGU/min, P < 0.01), and the response was almost fully reversible. When specimens were bathed with cyclooxygenase inhibitors flurbiprofen (10(-5) M) or flufenamic acid (10(-4) M), this macula densa-activated increase in renin release was largely or completely abolished (flurbiprofen, 3.5-10.5 nGU/min, not significant; flufenamic acid, 9.0-12.3 nGU/min, not significant). Exposing the macula densa to a step increase in perfusate NaCl concentration (low to high) resulted in a significant and reversible suppression of renin secretion in control specimens, but no significant suppression was seen in specimens treated with flufenamic acid. These data provide direct evidence to support the hypothesis that locally produced prostaglandins may act as a primary mediator of the renin response to macula densa activation.

scholarly journals Tubuloglomerular feedback and renin secretion in NTPDase1/CD39-deficient mice

2008 ◽  
Vol 294 (4) ◽  
pp. F965-F970 ◽  
Author(s):  
Mona Oppermann ◽  
David J. Friedman ◽  
Robert Faulhaber-Walter ◽  
Diane Mizel ◽  
Hayo Castrop ◽  
...  
Keyword(s):  
Signal Transmission ◽  
Critical Role ◽  
Juxtaglomerular Apparatus ◽  
Macula Densa ◽  
Renin Secretion ◽  
Tubuloglomerular Feedback ◽  
Salt Loading ◽  
Dependent Inhibition ◽  
Proximal Tubular ◽  
Deficient Mice

Studies in mice with null mutations of adenosine 1 receptor or ecto-5′-nucleotidase genes suggest a critical role of adenosine and its precursor 5′-AMP in tubulovascular signaling. To assess whether the source of juxtaglomerular nucleotides can be traced back to ATP dephosphorylation, experiments were performed in mice with a deficiency in NTPDase1/CD39, an ecto-ATPase catalyzing the formation of AMP from ATP and ADP. Urine osmolarity and glomerular filtration rate (GFR) were indistinguishable between NTPDase1/CD39−/− and wild-type (WT) mice. Maximum tubuloglomerular feedback (TGF) responses, as determined by proximal tubular stop flow pressure measurements, were reduced in NTPDase1/CD39−/− mice compared with controls (4.2 ± 0.9 vs. 10.5 ± 1.2 mmHg, respectively; P = 0.0002). Residual TGF responses gradually diminished after repeated changes in tubular perfusion flow averaging 2.9 ± 0.9 (on response) and 3.5 ± 1.1 (off response) mmHg after the second and 2.2 ± 0.5 (on response) and 1.5 ± 0.8 (off response) mmHg after the third challenge, whereas no fading of TGF responsiveness was observed in WT mice. Macula densa-dependent and pressure-dependent inhibition of renin secretion, as assessed by acute salt loading and phenylephrine injection, respectively, were intact in NTPDase1/CD39-deficient mice. In summary, NTPDase1/CD39-deficient mice showed a markedly compromised TGF regulation of GFR. These data support the concept of an extracellular dephosphorylation cascade during tubular-vascular signal transmission in the juxtaglomerular apparatus that is initiated by a regulated release of ATP from macula densa cells and results in adenosine-mediated afferent arteriole constriction.

scholarly journals Parathyroid hormone stimulates juxtaglomerular cell cAMP accumulation without stimulating renin release

2012 ◽  
Vol 303 (8) ◽  
pp. F1157-F1165 ◽  
Author(s):  
Douglas K. Atchison ◽  
Pamela Harding ◽  
M. Cecilia Ortiz-Capisano ◽  
Edward L. Peterson ◽  
William H. Beierwaltes
Keyword(s):  
Parathyroid Hormone ◽  
Primary Cultures ◽  
Positive Control ◽  
Renin Secretion ◽  
Renin Release ◽  
Intracellular Camp ◽  
Related Protein ◽  
Camp Content ◽  
Parathyroid Hormone Related Protein ◽  
Do So

Parathyroid hormone (PTH) is positively coupled to the generation of cAMP via its actions on the PTH1R and PTH2R receptors. Renin secretion from juxtaglomerular (JG) cells is stimulated by elevated intracellular cAMP, and every stimulus that increases renin secretion is thought to do so via increasing cAMP. Thus we hypothesized that PTH increases renin release from primary cultures of mouse JG cells by elevating intracellular cAMP via the PTH1R receptor. We found PTH1R, but not PTH2R, mRNA expressed in JG cells. While PTH increased JG cell cAMP content from (log10 means ± SE) 3.27 ± 0.06 to 3.92 ± 0.12 fmol/mg protein ( P < 0.001), it did not affect renin release. The PTH1R-specific agonist, parathyroid hormone-related protein (PTHrP), also increased JG cell cAMP from 3.13 ± 0.09 to 3.93 ± 0.09 fmol/mg protein ( P < 0.001), again without effect on renin release. PTH2R receptor agonists had no effect on cAMP or renin release. PTHrP increased cAMP in the presence of both low and high extracellular calcium from 3.31 ± 0.17 to 3.83 ± 0.20 fmol/mg protein ( P < 0.01) and from 3.29 ± 0.18 to 3.63 ± 0.22 fmol/mg protein ( P < 0.05), respectively, with no effect on renin release. PTHrP increased JG cell cAMP in the presence of adenylyl cyclase-V inhibition from 2.85 ± 0.17 to 3.44 ± 0.14 fmol/mg protein ( P < 0.001) without affecting renin release. As a positive control, forskolin increased JG cell cAMP from 3.39 ± 0.13 to 4.48 ± 0.07 fmol/mg protein ( P < 0.01) and renin release from 2.96 ± 0.10 to 3.29 ± 0.08 ng ANG I·mg prot−1·h−1 ( P < 0.01). Thus PTH increases JG cell cAMP via non-calcium-sensitive adenylate cyclases without affecting renin release. These data suggest compartmentalization of cAMP signaling in JG cells.

Inhibition of intrarenal NO stimulates renin secretion through a macula densa-mediated mechanism

1997 ◽  
Vol 272 (3) ◽  
pp. R879-R886 ◽  
Author(s):  
C. G. Schnackenberg ◽  
B. L. Tabor ◽  
M. H. Strong ◽  
J. P. Granger
Keyword(s):  
Kidney Function ◽  
Fractional Excretion ◽  
Macula Densa ◽  
Secretion Rate ◽  
Renin Secretion ◽  
Renin Release ◽  
Normal Kidney ◽  
Synthesis Inhibition ◽  
Normal Kidney Function ◽  
Fractional Excretion Of Sodium

Because endothelium-derived factors are known to have multiple actions throughout the body, the role of nitric oxide (NO) produced within the kidney in the regulation of renin release is still unclear. Therefore, the objectives of this study were to determine the effect of local NO synthesis inhibition within the kidney on renin secretion rate (RSR) and to determine whether the macula densa mechanism mediates the effect of NO on renin secretion rate in dogs. The NO synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) was administered via the renal artery at 5 microg x kg(-1) x min(-1) to dogs with normal kidney function and to dogs with the macula densa mechanism blocked, established by using the nonfiltering kidney model. In dogs with normal kidney function, renal arterial pressure (RAP) and glomerular filtration rate (GFR) remained constant throughout the experiment (131 +/- 5 mmHg and 22.6 +/- 3.0 ml/min, respectively). However, intrarenal NO synthesis inhibition decreased renal blood flow (RBF) by 16% (240 +/- 22 to 201 +/- 23 ml/min) and increased renal vascular resistance (RVR) by 24% (0.59 +/- 0.08 to 0.73 +/- 0.09 mmHg x ml(-1) x min). In addition, L-NAME decreased the fractional excretion of lithium by 27% (30.0 +/- 3.7 to 21.6 +/- 4.3%) and decreased the fractional excretion of sodium by 35% (0.86 +/- 0.29 to 0.56 +/- 0.21%). Associated with these changes in renal function, renin secretion rate increased by 194 and 235%. In marked contrast, renin secretion rate remained constant in dogs with the macula densa mechanism blocked. Intrarenal NO synthase blockade decreased RSR by 4 and 10% in dogs with the macula densa mechanism blocked. The RAP, RBF, and RVR responses to intrarenal NO synthesis inhibition in dogs with the macula densa mechanism blocked were similar to the renal hemodynamic response in dogs with normal kidney function. In summary, we have demonstrated that intrarenal NO synthesis blockade enhances renin secretion in dogs. The macula densa mechanism appears to play an important role in mediating the effect of intrarenal NO synthesis inhibition on renin release.

Inhibition of macula densa-stimulated renin secretion by pharmacological blockade of cyclooxygenase-2

1999 ◽  
Vol 277 (5) ◽  
pp. F706-F710 ◽  
Author(s):  
Timothy R. Traynor ◽  
Ann Smart ◽  
Josephine P. Briggs ◽  
Jurgen Schnermann
Keyword(s):  
Juxtaglomerular Apparatus ◽  
Macula Densa ◽  
Renin Secretion ◽  
Granular Cells ◽  
Cox Inhibitors ◽  
Nacl Concentration ◽  
Pharmacological Blockade ◽  
Cox 2 ◽  
Cox 1 ◽  
Stimulation Of

Previous results from our laboratory have shown that in the isolated perfused juxtaglomerular apparatus, nonselective inhibitors of cyclooxygenase (COX) activity prevent the stimulation of renin secretion by a reduction in luminal NaCl concentration at the macula densa. The present studies were performed to examine which COX isoform is involved in NaCl-dependent renin secretion. In the absence of COX inhibitors, a reduction in luminal NaCl (from Na 141/Cl 120 mM to Na 26/Cl 7 mM) caused an increase in renin secretion rate from 4.5 ± 1.8 to 26.1 ± 7.4 nGU/min ( P < 0.01, n = 19). The presence of the COX-1 inhibitor valerylsalicylate (500 μM) in lumen and bath did not affect the stimulation of renin secretion by a reduction in luminal NaCl concentration (5 ± 1.8 nGU/min at high NaCl, and 30.5 ± 9.4 nGU/min at low NaCl; P < 0.01, n = 8). In contrast, the specific COX-2 inhibitor NS-398 (50 μM) in lumen and bath abolished the stimulating effect of low luminal NaCl (12.8 ± 3.9 nGU/min at high NaCl, and 10.7 ± 3.1 nGU/min at low NaCl; NS, n = 15). The finding that COX-2 is critically involved in macula densa control of renin secretion indicates that the COX-2-expressing epithelial cells in the tubuloglomerular contact area are a likely source of prostaglandins participating in the signaling pathway between the macula densa and renin-producing granular cells.

Mechanism for inhibition of renin release by acute plasma volume expansion in the dog

1985 ◽  
Vol 248 (2) ◽  
pp. F206-F211 ◽  
Author(s):  
M. W. Roy ◽  
C. E. Ott ◽  
W. J. Welch ◽  
J. H. Downs ◽  
T. A. Kotchen
Keyword(s):  
Plasma Volume ◽  
Volume Expansion ◽  
Chloride Transport ◽  
Renin Secretion ◽  
Renin Release ◽  
Renal Nerves ◽  
Plasma Volume Expansion ◽  
Renal Nerve ◽  
Albumin Infusion ◽  
Renal Tubular

Plasma volume expansion alters renal tubular sodium chloride transport and renal nerve activity. The purpose of this study was to determine the mechanism(s) for inhibition of renin secretion by acute volume expansion with albumin in the anesthetized dog. In dogs with a single intact kidney, albumin infusion decreased renin release by 86% and significantly increased renal blood flow, glomerular filtration rate, and sodium excretion. Albumin volume expansion inhibited renin secretion to a lesser extent in dogs with denervated filtering kidneys and in dogs with innervated nonfiltering kidneys. In dogs with denervated nonfiltering kidneys, albumin infusion did not change renin secretion. Comparable volume expansion was produced in all groups. Thus, inhibition of renin release by acute plasma volume expansion is dependent on both a renal tubular mechanism and the integrity of the renal nerves. Partial inhibition of renin release was observed with interruption of either one of the mechanisms, whereas interruption of both mechanisms totally abolished the effect of acute plasma volume expansion on renin secretion.

Characterization of the macula densa stimulus for renin secretion

1990 ◽  
Vol 259 (1) ◽  
pp. F186-F193 ◽  
Author(s):  
J. N. Lorenz ◽  
H. Weihprecht ◽  
J. Schnermann ◽  
O. Skott ◽  
J. P. Briggs
Keyword(s):  
Flow Rate ◽  
Juxtaglomerular Apparatus ◽  
Macula Densa ◽  
Renin Secretion ◽  
Renal Nerve ◽  
Perfusate Flow ◽  
Nacl Concentration ◽  
Renal Nerve Activity ◽  
In Series ◽  
Concentration Changes

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.

The Immediate Plasma Renin Response to Propranolol: Evidence for a Different Mode of Renin Release in Essential and Renal Hypertension

1976 ◽  
Vol 51 (s3) ◽  
pp. 243s-245s
Author(s):  
F. Skrabal ◽  
W. Czaykowska ◽  
P. Dittrich ◽  
H. Braunsteiner
Keyword(s):  
Plasma Renin Activity ◽  
Dominant Role ◽  
Renal Hypertension ◽  
Plasma Renin ◽  
Juxtaglomerular Apparatus ◽  
Normal Subjects ◽  
Renin Secretion ◽  
Renin Activity ◽  
Renin Release ◽  
Intravenous Injections

1. The immediate short-term effects of intravenous injections of propranolol on plasma renin activity were studied in thirty-one normal subjects, 102 patients with benign essential and sixty-six patients with renal hypertension. 2. In essential hypertensive patients and normal subjects a marked fall in plasma renin activity was observed within 15 min, which was directly proportional to initial plasma renin values. In contrast, in patients with renal hypertension the fall observed was much less pronounced, or totally absent. 3. These differences in response to propranolol, which were particularly pronounced in patients with high initial renin values, suggest a dominant role of sympathetic tone at the juxtaglomerular apparatus for basal renin release in normal individuals and essential hypertensive subjects only. 4. The observations also indicate that sympathetic activity plays no part in the control of basal renin secretion in patients with renal hypertension, in whom basal renin secretion may be maintained by the renal baroreceptors.

Effects of adenosine and angiotensin on macula densa-stimulated renin secretion

1993 ◽  
Vol 265 (2) ◽  
pp. F187-F194 ◽  
Author(s):  
J. N. Lorenz ◽  
H. Weihprecht ◽  
X. R. He ◽  
O. Skott ◽  
J. P. Briggs ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Juxtaglomerular Apparatus ◽  
Inhibitory Effect ◽  
Macula Densa ◽  
Renin Secretion ◽  
Rabbit Kidney ◽  
Paracrine Factor ◽  
Adenosine Concentration ◽  
Nacl Concentration ◽  
High Concentrations

The present studies were performed to assess, in the isolated perfused juxtaglomerular apparatus of the rabbit kidney, the effect of exogenous adenosine on renin secretion stimulated by a low NaCl concentration at the macula densa. Addition of adenosine to the bath resulted in a change of renin secretion from 30.4 to 23.9 nGU/min at an adenosine concentration of 10(-6) M (n = 7; P = NS), from 38.6 to 17.9 nGU/min at a concentration of 10(-4) M (n = 7; P = 0.038), and from 18.4 to 5.8 nGU/min at 10(-2) M (P = 0.0053). Addition of the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine at 10(-5) M fully reversed the effect of adenosine at 10(-4) M, but not at 10(-2) M. Inhibition of adenosine breakdown by the adenosine deaminase inhibitor pentostatin (10(-6) M) enhanced the inhibitory effect of adenosine with renin secretion falling from 61.7 to 19.5 nGU/min at 10(-6) M adenosine (P = 0.035) and from 44.7 to 13.5 nGU/min at 10(-4) M adenosine (n = 0.027). A marked inhibition of NaCl-dependent renin secretion was caused by both angiotensin II (P = 0.011) and angiotensin III (P = 0.006), both at 10(-8) M. These results show that adenosine is capable of reducing macula densa-mediated renin secretion, but that this effect, even at very high concentrations or during adenosine deaminase blockade, does not fully mimic the inhibitory potency of increasing luminal NaCl concentration. Because the marked effect caused by angiotensins establishes the potential of this preparation to demonstrate inhibitory hormonal influences, it is concluded that adenosine does not appear to be the sole paracrine factor responsible for the NaCl-induced reduction of renin secretion.

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