Impaired responsiveness of renal mechanosensory nerves in heart failure: role of endogenous angiotensin

2003 ◽  
Vol 284 (1) ◽  
pp. R116-R124 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith
Keyword(s):  
Heart Failure ◽  
Substance P ◽  
Urinary Sodium Excretion ◽  
Ang Ii ◽  
Renal Nerve ◽  
High Sodium ◽  
Sodium Diet ◽  
P Release ◽  
Substance P Release ◽  
Pelvic Pressure

Increasing renal pelvic pressure results in PGE2-mediated release of substance P. Substance P increases afferent renal nerve activity (ARNA), which leads to a reflex increase in urinary sodium excretion (UNaV). Endogenous ANG II modulates the responsiveness of renal mechanosensory nerves. The ARNA and UNaV responses are suppressed by low- and enhanced by high-sodium diet. We examined whether the ARNA responses are altered in rats with congestive heart failure (CHF), a condition characterized by increased ANG II and sodium retention. The ARNA responses to increasing renal pelvic pressure ≤7.5 mmHg were suppressed in CHF vs. sham-CHF rats fed normal sodium diet. In CHF rats, increasing renal pelvic pressure 2.5 and 7.5 mmHg increased ARNA 0 ± 1 and 13 ± 2% ( P < 0.01) before and 9 ± 1 ( P < 0.01) and 19 ± 1% ( P < 0.01) during renal pelvic perfusion with losartan. Losartan had no effect on the ARNA responses in sham-CHF rats. In isolated renal pelvises from CHF rats, PGE2increased substance P release from 11 ± 2 to 15 ± 3 pg/min (not significant) without and from 16 ± 2 to 30 ± 4 pg/min ( P < 0.01) with losartan in the incubation bath. Losartan had no effect on PGE2-mediated substance P release in sham-CHF rats. In conclusion, the responsiveness of renal mechanosensory nerves is impaired in CHF rats due to ANG II inhibiting PGE2-mediated release of substance P from renal pelvic nerves.

Endogenous angiotensin modulates PGE2-mediated release of substance P from renal mechanosensory nerve fibers

2002 ◽  
Vol 282 (1) ◽  
pp. R19-R30 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith
Keyword(s):  
Substance P ◽  
Nerve Fibers ◽  
Ang Ii ◽  
High Sodium ◽  
Sodium Diet ◽  
Low Sodium Diet ◽  
Low Sodium ◽  
Pelvic Perfusion ◽  
High Sodium Diet ◽  
Pelvic Pressure

Increasing renal pelvic pressure increases afferent renal nerve activity (ARNA) by a prostaglandin E2(PGE2)-mediated release of substance P (SP) from renal pelvic sensory nerves. We examined whether the ARNA responses were modulated by high- and low-sodium diets. Increasing renal pelvic pressure resulted in greater ARNA responses in rats fed a high-sodium than in those fed a low-sodium diet. In rats fed a low-sodium diet, increasing renal pelvic pressure 2.5 and 7.5 mmHg increased ARNA 2 ± 1 and 13 ± 1% before and 12 ± 1 and 22 ± 2% during renal pelvic perfusion with 0.44 mM losartan. In rats fed a high-sodium diet, similar increases in renal pelvic pressure increased ARNA 10 ± 1 and 23 ± 3% before and 1 ± 1 and 11 ± 2% during pelvic perfusion with 15 nM ANG II. The PGE2-mediated release of SP from renal pelvic nerves in vitro was enhanced in rats fed a high-sodium diet and suppressed in rats fed a low-sodium diet. The PGE2 concentration required for SP release was 0.03, 0.14, and 3.5 μM in rats fed high-, normal-, and low-sodium diets. In rats fed a low-sodium diet, PGE2increased renal pelvic SP release from 5 ± 1 to 6 ± 1 pg/min without and from 12 ± 1 to 21 ± 2 pg/min with losartan in the incubation bath. Losartan had no effect on SP release in rats fed normal- and high-sodium diets. ANG II modulates the responsiveness of renal pelvic mechanosensory nerves by inhibiting PGE2-mediated SP release from renal pelvic nerve fibers.

scholarly journals Activation of endothelin A receptors contributes to impaired responsiveness of renal mechanosensory nerves in congestive heart failureThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

2010 ◽  
Vol 88 (6) ◽  
pp. 622-629 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Susan Y. Jones
Keyword(s):  
Substance P ◽  
Sensory Nerve ◽  
Reflex Response ◽  
Nerve Activity ◽  
Renal Nerve ◽  
P Release ◽  
Renal Nerve Activity ◽  
Pelvic Perfusion ◽  
Substance P Release ◽  
Pelvic Pressure

Increasing renal pelvic pressure results in PGE2-mediated release of substance P, leading to increases in afferent renal nerve activity (ARNA) and natriuresis, that is, a renorenal reflex response. The renorenal reflexes are impaired in congestive heart failure (CHF). Impairment of the renorenal reflexes may contribute to the increased renal sympathetic nerve activity and sodium retention in CHF. Endothelin (ET)-1 contributes to the pathological changes in cardiac and renal function in CHF. Therefore, we examined whether the ETA receptor antagonist BQ123 altered the responsiveness of renal mechanosensory nerves in CHF. The ARNA responses to increasing renal pelvic pressure were suppressed in CHF but not in sham-CHF rats. In CHF, increasing renal pelvic pressure by 7.5 mm Hg before and during renal pelvic perfusion with BQ123 increased ARNA 12% ± 3% and 21% ± 3% (p < 0.05 vs. vehicle). In isolated renal pelvises from CHF rats, PGE2 increased substance P release from 5 ± 0 to 7 ± 1 pg/min without BQ123 and from 4 ± 1 to 9 ± 1 pg/min with BQ123 in the bath (p < 0.01 vs. vehicle). BQ123 had no effect on the ARNA responses or substance P release in sham-CHF. In conclusion, activation of ETA receptors contributes to the impaired responsiveness of renal mechanosensory nerves in CHF rats by a mechanism(s) at the renal sensory nerve endings.

Bradykinin-mediated activation of renal sensory neurons due to prostaglandin-dependent release of substance P

1997 ◽  
Vol 272 (6) ◽  
pp. R2009-R2016 ◽  
Author(s):  
U. C. Kopp ◽  
D. M. Farley ◽  
L. A. Smith
Keyword(s):  
Substance P ◽  
Sensory Receptors ◽  
Nerve Activity ◽  
Renal Nerve ◽  
P Release ◽  
Renal Nerve Activity ◽  
Substance P Receptor ◽  
Pelvic Perfusion ◽  
Substance P Release ◽  
Substance P Receptors

In anesthetized rats, renal pelvic administration of bradykinin results in a prostaglandin (PG)-dependent increase in afferent renal nerve activity (ARNA). We now measured renal pelvic release of PGE and substance P during renal pelvic administration of bradykinin. Bradykinin increased ARNA and renal pelvic release of PGE by 497 +/- 252 pg/min and substance P. by 10.7 +/- 7.2 pg/min. Renal pelvic perfusion with indomethacin abolished the bradykinin-mediated increase in ARNA and reduced renal pelvic release of PGE and substance P by 76 +/- 11 and 72 +/- 8%, respectively. To examine whether the increased substance P release contributed to bradykinin-mediated activation of renal sensory receptors, renal pelvis was perfused with the substance P-receptor antagonists CP-96,345, CP-99,994, or RP-67580. The ARNA response to bradykinin was reduced 73 +/- 11, 55 +/- 12, and 64 +/- 10% by CP-96,345, CP-99,994, and RP-67580, respectively. The inactive enantiomers CP-96,344 and RP-68651 had no effect. These data suggest that bradykinin increases renal pelvic release of PGE, which facilitates the release of substance P, which in turn stimulates substance P receptors. Thus the ARNA response to bradykinin is largely mediated by activation of substance P receptors.

scholarly journals Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α2-adrenoceptors on renal sensory nerves

2011 ◽  
Vol 300 (2) ◽  
pp. R298-R310 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith ◽  
Saku Ruohonen ◽  
Mika Scheinin ◽  
...  
Keyword(s):  
Substance P ◽  
Sodium Intake ◽  
Sensory Nerves ◽  
Nerve Activity ◽  
Renal Nerve ◽  
High Sodium ◽  
Sodium Diet ◽  
Low Sodium ◽  
Renal Nerve Activity ◽  
High Sodium Diet

Activation of efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which then reflexively decreases ERSNA via activation of the renorenal reflexes to maintain low ERSNA. The ERSNA-ARNA interaction is mediated by norepinephrine (NE) that increases and decreases ARNA by activation of renal α1-and α2-adrenoceptors (AR), respectively. The ERSNA-induced increases in ARNA are suppressed during a low-sodium (2,470 ± 770% s) and enhanced during a high-sodium diet (5,670 ± 1,260% s). We examined the role of α2-AR in modulating the responsiveness of renal sensory nerves during low- and high-sodium diets. Immunohistochemical analysis suggested the presence of α2A-AR and α2C-AR subtypes on renal sensory nerves. During the low-sodium diet, renal pelvic administration of the α2-AR antagonist rauwolscine or the AT1 receptor antagonist losartan alone failed to alter the ARNA responses to reflex increases in ERSNA. Likewise, renal pelvic release of substance P produced by 250 pM NE (from 8.0 ± 1.3 to 8.5 ± 1.6 pg/min) was not affected by rauwolscine or losartan alone. However, rauwolscine+losartan enhanced the ARNA responses to reflex increases in ERSNA (4,680 ± 1,240%·s), and renal pelvic release of substance P by 250 pM NE, from 8.3 ± 0.6 to 14.2 ± 0.8 pg/min. During a high-sodium diet, rauwolscine had no effect on the ARNA response to reflex increases in ERSNA or renal pelvic release of substance P produced by NE. Losartan was not examined because of low endogenous ANG II levels in renal pelvic tissue during a high-sodium diet. Increased activation of α2-AR contributes to the reduced interaction between ERSNA and ARNA during low-sodium intake, whereas no/minimal activation of α2-AR contributes to the enhanced ERSNA-ARNA interaction under conditions of high sodium intake.

Impaired substance P release from renal sensory nerves in SHR involves a pertussis toxin-sensitive mechanism

2004 ◽  
Vol 286 (2) ◽  
pp. R326-R333 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha
Keyword(s):  
Substance P ◽  
Pertussis Toxin ◽  
Sensory Nerves ◽  
Ang Ii ◽  
Spontaneously Hypertensive ◽  
P Release ◽  
Pelvic Wall ◽  
Wistar Kyoto ◽  
Pka Pathway ◽  
Substance P Release

Stretching the renal pelvic wall activates renal mechanosensory nerves by a PGE2-mediated release of substance P via activation of the cAMP-PKA pathway. Renal pelvic ANG II modulates the responsiveness of renal sensory nerves by suppressing the PGE2-mediated activation of adenylyl cyclase via a pertussis toxin (PTX)-sensitive mechanism. In SHR, activation of renal mechanosensory nerves is impaired. This is due to suppressed release of substance P in response to increased pelvic pressure. The present study was performed to investigate whether the PGE2-mediated release of substance P was suppressed in SHR vs. WKY and, if so, whether the impaired PGE2-mediated release of substance P was due to ANG II activating a PTX-sensitive mechanism. In an isolated renal pelvic wall preparation, PGE2, 0.14 μM, increased substance P release from 9 ± 3 to 22 ± 3 pg/min ( P < 0.01) in Wistar-Kyoto rats (WKY), but had no effect in spontaneously hypertensive rats (SHR). A tenfold higher concentration of PGE2, 1.4 μM, was required to increase substance P release in SHR, from 7 ± 1 to 22 ± 3 pg/min ( P < 0.01). In SHR, treating renal pelvises with losartan enhanced the release of substance P produced by subthreshold concentration of PGE2, 0.3 μM, from 16 ± 2 to 26 ± 3 pg/min ( P < 0.01). Likewise, treating renal pelvises with PTX enhanced the PGE2-mediated release of substance P from 10 ± 1 to 33 ± 3 pg/min ( P < 0.01) in SHR. In WKY, neither losartan nor PTX had an effect on the release of substance P produced by subthreshold concentrations of PGE2, 0.03 μM. In conclusion, the impaired responsiveness of renal sensory nerves in SHR involves endogenous ANG II suppressing the PGE2-mediated release of substance P via a PTX-sensitive mechanism.

Angiotensin blocks substance P release from renal sensory nerves by inhibiting PGE2-mediated activation of cAMP

2003 ◽  
Vol 285 (3) ◽  
pp. F472-F483 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith
Keyword(s):  
Substance P ◽  
Area Under The Curve ◽  
Inhibitory Effect ◽  
Sensory Nerves ◽  
Ang Ii ◽  
Renal Nerve ◽  
High Sodium ◽  
Renal Nerve Activity ◽  
Pka Pathway

Activation of renal sensory nerves involves PGE2-mediated release of substance P (SP) via activation of the cAMP-PKA pathway. The PGE2-mediated SP release is suppressed by a low- and enhanced by a high-sodium (Na+) diet, suggesting an inhibitory effect of ANG. We now examined whether ANG II is present in the pelvic wall and inhibits PGE2-mediated SP release by blocking PGE2-mediated increases in cAMP. ANG II levels in renal pelvic tissue were 710 ± 95 and 260 ± 30 fmol/g tissue in rats fed a low- and high-Na+ diet, respectively. In a renal pelvic preparation from high-Na+-diet rats, 0.14 μM PGE2 produced an increase in SP release from 7 ± 1 to 19 ± 3 pg/min that was blocked by 15 nM ANG II. Treating pelvises with pertussis toxin (PTX) abolished the effects of ANG II. In pelvises from low-Na+ rats, neither basal nor bradykinin-mediated SP release was altered by PGE2. However, the bradykinin-mediated release of SP was enhanced by the permeable cAMP analog CPT-cAMP, from 4 ± 1 to 11 ± 2 pg/min, a response similar to that in normal-Na+-diet rats. In vivo, renal pelvic administration of PGE2 enhanced the afferent renal nerve activity (ARNA) response to bradykinin in normal- but not in low-Na+ diet rats. CPT-cAMP produced similar enhancement of the ARNA responses to bradykinin in normal- and low-Na+-diet rats, 1,670 ± 490 and 1,760 ± 400%·s (area under the curve of ARNA vs. time). Similarly, the ARNA responses to increases in renal pelvic pressure were similarly enhanced by CPT-cAMP in normal- and low-Na+-diet rats. In conclusion, renal pelvic ANG II modulates the responsiveness of renal sensory nerves by suppressing PGE2-mediated activation of adenylyl cyclase via a PTX-sensitive mechanism.

scholarly journals Dietary sodium modulates the interaction between efferent renal sympathetic nerve activity and afferent renal nerve activity: role of endothelin

2009 ◽  
Vol 297 (2) ◽  
pp. R337-R351 ◽  
Author(s):  
Ulla C. Kopp ◽  
Olaf Grisk ◽  
Michael Z. Cicha ◽  
Lori A. Smith ◽  
Antje Steinbach ◽  
...  
Keyword(s):  
Substance P ◽  
Dietary Sodium ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
P Release ◽  
Pelvic Wall ◽  
Renal Nerve Activity ◽  
Substance P Release

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which in turn decreases ERSNA via activation of the renorenal reflexes in the overall goal of maintaining low ERSNA. We now examined whether the ERSNA-induced increases in ARNA are modulated by dietary sodium and the role of endothelin (ET). The ARNA response to reflex increases in ERSNA was enhanced in high (HNa)- vs. low-sodium (LNa) diet rats, 7,560 ± 1,470 vs. 900 ± 390%·s. The norepinephrine (NE) concentration required to increase PGE2 and substance P release from isolated renal pelvises was 10 pM in HNa and 6,250 pM in LNa diet rats. In HNa diet pelvises 10 pM NE increased PGE2 release from 67 ± 6 to 150 ± 13 pg/min and substance P release from 6.7 ± 0.8 to 12.3 ± 1.8 pg/min. In LNa diet pelvises 6,250 pM NE increased PGE2 release from 64 ± 5 to 129 ± 22 pg/min and substance P release from 4.5 ± 0.4 to 6.6 ± 0.7 pg/min. In the renal pelvic wall, ETB-R are present on unmyelinated Schwann cells close to the afferent nerves and ETA-R on smooth muscle cells. ETA-receptor (R) protein expression in the renal pelvic wall is increased in LNa diet. In HNa diet, renal pelvic administration of the ETB-R antagonist BQ788 reduced ERSNA-induced increases in ARNA and NE-induced release of PGE2 and substance P. In LNa diet, the ETA-R antagonist BQ123 enhanced ERSNA-induced increases in ARNA and NE-induced release of substance P without altering PGE2 release. In conclusion, activation of ETB-R and ETA-R contributes to the enhanced and suppressed interaction between ERSNA and ARNA in conditions of HNa and LNa diet, respectively, suggesting a role for ET in the renal control of ERSNA that is dependent on dietary sodium.

PGE2 increases substance P release from renal pelvic sensory nerves via activation of N-type calcium channels

1999 ◽  
Vol 276 (5) ◽  
pp. R1241-R1248 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha
Keyword(s):  
Substance P ◽  
Calcium Channels ◽  
Sensory Nerves ◽  
Calcium Dependent ◽  
P Release ◽  
Calcium Blocker ◽  
Pelvic Wall ◽  
Substance P Release ◽  
Pelvic Pressure ◽  
Dependent Mechanism

Activation of renal pelvic sensory nerves by increased pelvic pressure results in a renal pelvic release of substance P that is dependent on intact prostaglandin synthesis. An isolated renal pelvic wall preparation was used to examine whether PGE2increases the release of substance P from renal pelvic sensory nerves and by what mechanisms. The validity of the model was tested by examining whether 50 mM KCl increased substance P release from the pelvic wall. Fifty millimolar KCl produced an increase in substance P release, from 9.6 ± 1.6 to 26.8 ± 4.0 pg/min, P < 0.01, that was blocked by the L-type calcium blocker verapamil (10 μM). PGE2 (0.14 μM) increased the release of substance P from the pelvic wall from 8.9 ± 0.9 to 20.6 ± 3.3 pg/min, P < 0.01. PGE2 failed to increase substance P release in a calcium-free medium. The PGE2-induced substance P release was blocked by the N-type calcium blocker ω-conotoxin (0.1 μM) but was unaffected by verapamil. In conclusion, PGE2 increases the release of substance P from renal pelvic sensory nerves by a calcium-dependent mechanism that requires influx of calcium via N-type calcium channels.

Differential effects of endothelin on activation of renal mechanosensory nerves: stimulatory in high-sodium diet and inhibitory in low-sodium diet

2006 ◽  
Vol 291 (5) ◽  
pp. R1545-R1556 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith
Keyword(s):  
Substance P ◽  
Dietary Intake ◽  
Sensory Nerves ◽  
High Sodium ◽  
Sodium Diet ◽  
Low Sodium Diet ◽  
Low Sodium ◽  
Salt Sensitive Hypertension ◽  
High Sodium Diet ◽  
Pelvic Pressure

Activation of renal mechanosensory nerves is enhanced by high and suppressed by low sodium dietary intake. Afferent renal denervation results in salt-sensitive hypertension, suggesting that activation of the afferent renal nerves contributes to water and sodium balance. Another model of salt-sensitive hypertension is the endothelin B receptor (ETBR)-deficient rat. ET and its receptors are present in sensory nerves. Therefore, we examined whether ET receptor blockade altered the responsiveness of the renal sensory nerves. In anesthetized rats fed high-sodium diet, renal pelvic administration of the ETBR antagonist BQ-788 reduced the afferent renal nerve activity (ARNA) response to increasing renal pelvic pressure 7.5 mmHg from 26 ± 3 to 9 ± 3% and the PGE2-mediated renal pelvic release of substance P from 9 ± 1 to 3 ± 1 pg/min. Conversely, in rats fed low-sodium diet, renal pelvic administration of the ETAR antagonist BQ-123 enhanced the ARNA response to increased renal pelvic pressure from 9 ± 2 to 23 ± 6% and the PGE2-mediated renal pelvic release of substance P from 0 ± 0 to 6 ± 1 pg/min. Adding the ETAR antagonist to ETBR-blocked renal pelvises restored the responsiveness of renal sensory nerves in rats fed a high-sodium diet. Adding the ETBR antagonist to ETAR-blocked pelvises suppressed the responsiveness of the renal sensory nerves in rats fed a low-sodium diet. In conclusion, activation of ETBR and ETAR contributes to the enhanced and suppressed responsiveness of renal sensory nerves in conditions of high- and low-sodium dietary intake, respectively. Impaired renorenal reflexes may contribute to the salt-sensitive hypertension in the ETBR-deficient rat.

scholarly journals Impaired responsiveness of renal sensory nerves in streptozotocin-treated rats and obese Zucker diabetic fatty rats: role of angiotensin

2008 ◽  
Vol 294 (3) ◽  
pp. R858-R866 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Mark A. Yorek
Keyword(s):  
Substance P ◽  
Renin Angiotensin System ◽  
Sensory Nerves ◽  
Nerve Activity ◽  
Renal Nerve ◽  
P Release ◽  
Zucker Diabetic Fatty Rats ◽  
Renal Nerve Activity ◽  
Zdf Rats ◽  
Substance P Release

Increasing afferent renal nerve activity decreases efferent renal nerve activity and increases urinary sodium excretion. Activation of renal pelvic mechanosensory nerves is impaired in streptozotocin (STZ)-treated rats (model of type 1 diabetes). Decreased activation of renal sensory nerves would lead to increased efferent renal nerve activity, sodium retention, and hypertension. We examined whether the reduced activation of renal sensory nerves in STZ rats was due to increased renal angiotensin activity and whether activation of the renal sensory nerves was impaired in obese Zucker diabetic fatty (ZDF) rats (model of type 2 diabetes). In an isolated renal pelvic wall preparation from rats treated with STZ for 2 wk, PGE2 failed to increase the release of substance P, from 5 ± 1 to 6 ± 1 pg/min. In pelvises from sham STZ rats, PGE2 increased substance P release from 6 ± 1 to 13 ± 2 pg/min. Adding losartan to the incubation bath increased PGE2-mediated release of substance P in STZ rats, from 5 ± 1 to 10 ± 2 pg/min, but had no effect in sham STZ rats. In pelvises from obese ZDF rats (22–46 wk old), PGE2 increased substance P release from 12.0 ± 1.2 to 18.3 ± 1.2 pg/min, which was less than that from lean ZDF rats (10.3 ± 1.6 to 22.5 ± 2.4 pg/min). Losartan had no effect on the PGE2-mediated substance P release in obese or lean ZDF rats. We conclude that the mechanisms involved in the decreased responsiveness of the renal sensory nerves in STZ rats involve activation of the renin angiotensin system in STZ but not in obese ZDF rats.

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