Abstract 476: Renal Sensory Reinnervation Following Acute Renal Denervation.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Ulla Kopp ◽  
Jan Mulder ◽  
Tomas Hölt ◽  
Mark M Knuepfer
Keyword(s):  
Substance P ◽  
Optical Density ◽  
Renal Denervation ◽  
Blood Pressure Reduction ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Sensory Innervation ◽  
Multiple Time ◽  
Pelvic Wall ◽  
Sensory Reinnervation

It is known that efferent sympathetic nerves reinnervate the kidney following renal denervation (DNX). As there is evidence for lack of cardiac sensory reinnervation following heart transplantation, it has been thought that renal sensory nerves do not reinnervate following renal DNX. This absence of renal sensory reinnervation has been suggested to contribute to the chronic blood pressure reduction (3 years) in humans following renal DNX. However, whether renal sensory reinnervation occurs following acute renal DNX has not been thoroughly examined. Therefore, we assessed renal sensory innervation at multiple time points from 4 days to 12 wks following unilateral surgical DNX + application of phenol to the renal artery in normal Sprague Dawley rats. The contralateral innervated (INN) kidney served as control. Sensory innervation was determined as optical density (ImageJ) of the sensory nerves identified by immunohistochemistry using antibodies against the neuropeptides substance P and calcitonin-gene-related peptide (CGRP) in the renal pelvic wall, as it is a major site of renal sensory innervation. In INN kidneys, optical density of the sensory nerve fibers in the renal pelvic wall was unchanged over the 4 days - 12 wk period (n=17). In DNX kidneys, optical density of the substance P/CGRP containing sensory nerves was 3%, 30%, 50 % and 100% of the control contralateral INN kidney at 4 days, 2 wks, 4 wks and 12 wks, respectively, after DNX. Linear regression of optical density (DNX/INN) versus time yielded similar intercept and slope values for the substance P and CGRP containing sensory nerves (R 2 = 0.82 and 0.77, respectively, P<0.001 for both). Conclusion: in normal rats, sensory reinnervation of the renal pelvic wall is complete at 12 wks following acute surgical renal DNX.

scholarly journals Renal sensory and sympathetic nerves reinnervate the kidney in a similar time-dependent fashion after renal denervation in rats

2013 ◽  
Vol 304 (8) ◽  
pp. R675-R682 ◽  
Author(s):  
Jan Mulder ◽  
Tomas Hökfelt ◽  
Mark M. Knuepfer ◽  
Ulla C. Kopp
Keyword(s):  
Substance P ◽  
Optical Density ◽  
Renal Denervation ◽  
Time Course ◽  
Sympathetic Nerves ◽  
Sensory Nerves ◽  
Sensory Innervation ◽  
Multiple Time ◽  
Sensory Reinnervation ◽  
Renal Sympathetic

Efferent renal sympathetic nerves reinnervate the kidney after renal denervation in animals and humans. Therefore, the long-term reduction in arterial pressure following renal denervation in drug-resistant hypertensive patients has been attributed to lack of afferent renal sensory reinnervation. However, afferent sensory reinnervation of any organ, including the kidney, is an understudied question. Therefore, we analyzed the time course of sympathetic and sensory reinnervation at multiple time points (1, 4, and 5 days and 1, 2, 3, 4, 6, 9, and 12 wk) after renal denervation in normal Sprague-Dawley rats. Sympathetic and sensory innervation in the innervated and contralateral denervated kidney was determined as optical density (ImageJ) of the sympathetic and sensory nerves identified by immunohistochemistry using antibodies against markers for sympathetic nerves [neuropeptide Y (NPY) and tyrosine hydroxylase (TH)] and sensory nerves [substance P and calcitonin gene-related peptide (CGRP)]. In denervated kidneys, the optical density of NPY-immunoreactive (ir) fibers in the renal cortex and substance P-ir fibers in the pelvic wall was 6, 39, and 100% and 8, 47, and 100%, respectively, of that in the contralateral innervated kidney at 4 days, 4 wk, and 12 wk after denervation. Linear regression analysis of the optical density of the ratio of the denervated/innervated kidney versus time yielded similar intercept and slope values for NPY-ir, TH-ir, substance P-ir, and CGRP-ir fibers (all R2 > 0.76). In conclusion, in normotensive rats, reinnervation of the renal sensory nerves occurs over the same time course as reinnervation of the renal sympathetic nerves, both being complete at 9 to 12 wk following renal denervation.

PGE2 increases release of substance P from renal sensory nerves by activating the cAMP-PKA transduction cascade

2002 ◽  
Vol 282 (6) ◽  
pp. R1618-R1627 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith
Keyword(s):  
Substance P ◽  
Area Under The Curve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Renal Nerve ◽  
Pelvic Wall ◽  
Pelvic Nerves ◽  
Renal Nerve Activity ◽  
Pka Pathway ◽  
Pelvic Pressure

Increasing renal pelvic pressure increases afferent renal nerve activity (ARNA) by a PGE2-mediated release of substance P (SP) from renal pelvic nerves. The role of cAMP activation in the PGE2-mediated release of SP was studied by examining the effects of the adenylyl cyclase (AC) activator forskolin and AC inhibitor dideoxyadenosine (DDA). Forskolin enhanced the bradykinin-mediated release of SP from an isolated rat renal pelvic wall preparation, from 7.3 ± 1.3 to 15.6 ± 3.0 pg/min. PGE2 at a subthreshold concentration for SP release mimicked the effects of forskolin. The EP2 receptor agonist butaprost, 15 μM, and PGE2, 0.14 μM, produced similar increases in SP release, from 5.8 ± 0.8 to 17.0 ± 2.3 pg/min and from 8.0 ± 1.3 to 21.6 ± 2.7 pg/min. DDA blocked the SP release produced by butaprost and PGE2. The PGE2-induced release of SP was also blocked by the PKA inhibitors PKI14–22 and H-89. Studies in anesthetized rats showed that renal pelvic administration of butaprost, 10 μM, and PGE2, 0.14 μM, resulted in similar ARNA responses, 1,520 ± 390 and 1,170 ± 270% · s (area under the curve of ARNA vs. time) that were blocked by DDA. Likewise, the ARNA response to increased renal pelvic pressure, 7,180 ± 710% · s, was blocked by DDA. In conclusion, PGE2activates the cAMP-PKA pathway leading to a release of SP and activation of renal pelvic mechanosensory nerve fibers.

scholarly journals Early postnatal exposure of mice to side-steam tobacco smoke increases neuropeptide Y in lung

2012 ◽  
Vol 302 (1) ◽  
pp. L152-L159 ◽  
Author(s):  
Z.-X. Wu ◽  
K. B. Benders ◽  
D. D. Hunter ◽  
R. D. Dey
Keyword(s):  
Smooth Muscle ◽  
Neuropeptide Y ◽  
Tobacco Smoke ◽  
Early Life ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Sensory Innervation ◽  
Tracheal Smooth Muscle ◽  
Exposure Group ◽  
Postnatal Exposure

Our recent study showed that prenatal and early postnatal exposure of mice to side-steam tobacco smoke (SS), a surrogate to environmental tobacco smoke (ETS), leads to increased airway responsiveness and sensory innervation later in life. However, the underlying mechanism initiated in early life that affects airway responses later in life remains undefined. The concomitant increase in nerve growth factor (NGF) after exposures suggests that NGF may be involved the regulation of airway innervation. Since NGF regulates sympathetic nerve responses, as well as sensory nerves, we extended previous studies by examining neuropeptide Y (NPY), a neuropeptide associated with sympathetic nerves. Different age groups of mice, postnatal day (PD) 2 and PD21, were exposed to either SS or filtered air (FA) for 10 consecutive days. The level of NPY protein in lung and the density of NPY nerve fibers in tracheal smooth muscle were significantly increased in the PD2–11SS exposure group compared with PD2–11FA exposure. At the same time, the level of NGF in lung tissue was significantly elevated in the PD2–11SS exposure groups. However, neither NPY (protein or nerves) nor NGF levels were significantly altered in PD21–30SS exposure group compared with the PD21–30FA exposure group. Furthermore, pretreatment with NGF antibody or K252a, which inhibits a key enzyme (tyrosine kinase) in the transduction pathway for NGF receptor binding, significantly diminished SS-enhanced NPY tracheal smooth muscle innervation and the increase in methacholine-induced airway resistance. These findings show that SS exposure in early life increases NPY tracheal innervation and alters pulmonary function and that these changes are mediated through the NGF.

Renal sympathetic nerve activity modulates afferent renal nerve activity by PGE2-dependent activation of α1- and α2-adrenoceptors on renal sensory nerve fibers

2007 ◽  
Vol 293 (4) ◽  
pp. R1561-R1572 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith ◽  
Jan Mulder ◽  
Tomas Hökfelt
Keyword(s):  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Pelvic Wall ◽  
Renal Nerve Activity ◽  
Pelvic Perfusion ◽  
Renal Sympathetic

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA). To test whether the ERSNA-induced increases in ARNA involved norepinephrine activating α-adrenoceptors on the renal sensory nerves, we examined the effects of renal pelvic administration of the α1- and α2-adrenoceptor antagonists prazosin and rauwolscine on the ARNA responses to reflex increases in ERSNA (placing the rat's tail in 49°C water) and renal pelvic perfusion with norepinephrine in anesthetized rats. Hot tail increased ERSNA and ARNA, 6,930 ± 900 and 4,870 ± 670%·s (area under the curve ARNA vs. time). Renal pelvic perfusion with norepinephrine increased ARNA 1,870 ± 210%·s. Immunohistochemical studies showed that the sympathetic and sensory nerves were closely related in the pelvic wall. Renal pelvic perfusion with prazosin blocked and rauwolscine enhanced the ARNA responses to reflex increases in ERSNA and norepinephrine. Studies in a denervated renal pelvic wall preparation showed that norepinephrine increased substance P release, from 8 ± 1 to 16 ± 1 pg/min, and PGE2 release, from 77 ± 11 to 161 ± 23 pg/min, suggesting a role for PGE2 in the norepinephrine-induced activation of renal sensory nerves. Prazosin and indomethacin reduced and rauwolscine enhanced the norepinephrine-induced increases in substance P and PGE2. PGE2 enhanced the norepinephrine-induced activation of renal sensory nerves by stimulation of EP4 receptors. Interaction between ERSNA and ARNA is modulated by norepinephrine, which increases and decreases the activation of the renal sensory nerves by stimulating α1- and α2-adrenoceptors, respectively, on the renal pelvic sensory nerve fibers. Norepinephrine-induced activation of the sensory nerves is dependent on renal pelvic synthesis/release of PGE2.

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.

Prevention of cerebral vasospasm in the rat by depletion or inhibition of substance P in conducting vessels

1990 ◽  
Vol 72 (6) ◽  
pp. 917-925 ◽  
Author(s):  
Tia Juana Delgado-Zygmunt ◽  
Mohammed Abdul-Rahman Arbab ◽  
Lars Edvinsson ◽  
Inger Jansen ◽  
Niels Aage Svendgaard
Keyword(s):  
Substance P ◽  
Nucleus Tractus Solitarius ◽  
Cerebral Arteries ◽  
Intrathecal Administration ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Content Type ◽  
Substance P Antagonist ◽  
Reflex Arc ◽  
Blood Injection

✓ Cisternal blood injection in the rat induces a biphasic angiographic vasospasm, with a maximal acute spasm at 10 minutes and a maximal late spasm at 2 days after the subarachnoid hemorrhage (SAH). Depletion of substance P-containing sensory nerves to the cerebral arteries with capsaicin prior to SAH prevents the development of both acute and late spasm. Intrathecal administration of the substance P antagonist spantide 2 hours prior to SAH also prevents the development of vasospasm, while spantide administration 1 hour before SAH only hinders the occurrence of late vasospasm. Intracisternal administration of spantide 2 hours post-SAH prevents the development of late vasospasm. This antagonist per se can induce a short-lasting dose-dependent angiographic vasoconstriction. Substance P-containing nerve fibers on the cerebral arteries could constitute the sensory link in a reflex arc system involved in the development of vasospasm in which the presence of blood in the subarachnoid space stimulates sensory substance P-containing nerve fibers on the cerebral arteries inducing a centripetal impulse to the A2-nucleus tractus solitarius and setting into motion the events in the brain stem leading to acute and late vasospasm.

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.

Nitric oxide modulates renal sensory nerve fibers by mechanisms related to substance P receptor activation

2001 ◽  
Vol 281 (1) ◽  
pp. R279-R290 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith ◽  
Tomas Hökfelt
Keyword(s):  
Nitric Oxide ◽  
Substance P ◽  
Sensory Nerve ◽  
Receptor Activation ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Renal Nerve ◽  
Inhibitory Neurotransmitter ◽  
Pelvic Perfusion ◽  
Pelvic Pressure

Nerve terminals containing neuronal nitric oxide synthase (nNOS) are localized in the renal pelvic wall where the sensory nerves containing substance P and calcitonin gene-related peptide (CGRP) are found. We examined whether nNOS is colocalized with substance P and CGRP. All renal pelvic nerve fibers that contained nNOS-like immunoreactivity (-LI) also contained substance P-LI and CGRP-LI. In anesthetized rats, renal pelvic perfusion with the nNOS inhibitor S-methyl-l-thiocitrulline (l-SMTC, 20 μM) prolonged the afferent renal nerve activity (ARNA) response to a 3-min period of increased renal pelvic pressure from 5 ± 0.4 to 21 ± 2 min ( P < 0.01, n = 14). The magnitude of the ARNA response was unaffected byl-SMTC. Similar effects were produced by N ω-nitro-l-arginine methyl ester (l-NAME) but not d-NAME. Increasing renal pelvic pressure produced similar increases in renal pelvic release of substance P before and during l-SMTC, from 5.9 ± 1.4 to 13.6 ± 4.2 pg/min before and from 4.9 ± to 12.6 ± 2.7 pg/min during l-SMTC. l-SMTC also prolonged the ARNA response to renal pelvic perfusion with substance P (3 μM) from 1.2 ± 0.2 to 5.6 ± 1.1 min ( P < 0.01, n = 9) without affecting the magnitude of the ARNA response. In conclusion: activation of NO may function as an inhibitory neurotransmitter regulating the activation of renal mechanosensory nerve fibers by mechanisms related to activation of substance P receptors.

scholarly journals Serpinin in the Skin

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 183
Author(s):  
Cristina Fraquelli ◽  
Jasmine Hauzinger ◽  
Christian Humpel ◽  
Maria Nolano ◽  
Vincenzo Provitera ◽  
...  
Keyword(s):  
Substance P ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Molecular Form ◽  
Proteolytic Processing ◽  
Sensory Nerves ◽  
Sensory Innervation ◽  
Autonomic Nerves ◽  
Rat Skin ◽  
Highly Active

The serpinins are relatively novel peptides generated by proteolytic processing of chromogranin A and they are comprised of free serpinin, serpinin-RRG and pGlu-serpinin. In this study, the presence and source of these peptides were studied in the skin. By Western blot analysis, a 40 kDa and a 50 kDa protein containing the sequence of serpinin were detected in the trigeminal ganglion and dorsal root ganglia in rats but none in the skin. RP-HPLC followed by EIA revealed that the three serpinins are present in similar, moderate amounts in rat dorsal root ganglia, whereas in the rat skin, free serpinin represents the predominant molecular form. There were abundant serpinin-positive cells in rat dorsal root ganglia and colocalization with substance P was evident. However, much more widespread distribution of the serpinins was found in dorsal root ganglia when compared with substance P. In the skin, serpinin immunoreactivity was found in sensory nerves and showed colocalization with substance P; as well, some was present in autonomic nerves. Thus, although not exclusively, there is evidence that serpinin is a constituent of the sensory innervation of the skin. The serpinins are biologically highly active and might therefore be of functional significance in the skin.

Mast cell-nerve fiber interaction: Ultrastructural studies

1990 ◽  
Vol 48 (3) ◽  
pp. 428-429
Author(s):  
E.Y. Chi ◽  
M.L. Su ◽  
Y.T. Tien ◽  
W.R. Henderson
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Substance P ◽  
Nerve Fiber ◽  
Sensory Nerves ◽  
Ultrastructural Studies ◽  
Morphological Studies ◽  
Granulocyte Infiltration ◽  
Intracutaneous Injection ◽  
Recent Attention

Recent attention has been directed to the interaction of the nerve and immune systems. The neuropeptide substance P, a tachykinnin which is a neurotransmitter in the central and peripheral nervous systems produces tissue swelling, augemntation of intersitial fibrin deposition and leukocyte infiltration after intracutaneous injection. There is a direct correlation reported between the extent of mast cell degranulation at the sites of injection and the tissue swelling or granulocyte infiltration. It has previously been demonstrated that antidromic electrical stimulation of sensory nerves induces degranulation of cutaneous mast cells, cutaneous vasodilation and augmented vascular permeability. Morphological studies have documented a close anatiomical association between mast cells and nonmyelinated nerves, that contain substance P and other neuropeptides. However, the presence of mast cells within nerve fasicles has not been previously examined ultrastructurally. In this study, we examined ultrastructurally the distribution of mast cells in the nerve fiber bundles located in the muscular connective tissue of rat tongues (n=20).

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