| 1. |
- Kopp, UC, et al.
(författare)
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Activation of EP4 receptors contributes to prostaglandin E2-mediated stimulation of renal sensory nerves
- 2004
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Ingår i: American journal of physiology. Renal physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 287:6, s. F1269-F1282
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Tidskriftsartikel (refereegranskat)abstract
- Induction of cyclooxygenase-2 (COX-2) in the renal pelvic wall increases prostaglandin E2(PGE2) leading to stimulation of cAMP production, which results in substance P (SP) release and activation of renal mechanosensory nerves. The subtype of PGE receptors involved, EP2 and/or EP4, was studied by immunohistochemistry and renal pelvic administration of agonists and antagonists of EP2 and EP4 receptors. EP4 receptor-like immunoreactivity (LI) was colocalized with calcitonin gene-related peptide (CGRP)-LI in dorsal root ganglia (DRGs) at Th9-L1and in nerve terminals in the renal pelvic wall. Th9-L1DRG neurons also contained EP3 receptor-LI and COX-2-LI, each of which was colocalized with CGRP-LI in some neurons. No renal pelvic nerves contained EP3 receptor-LI and only very few nerves COX-2-LI. The EP1/EP2 receptor antagonist AH-6809 (20 μM) had no effect on SP release produced by PGE2(0.14 μM) from an isolated rat renal pelvic wall preparation. However, the EP4 receptor antagonist L-161,982 (10 μM) blocked the SP release produced by the EP2/EP4 receptor agonist butaprost (10 μM) 12 ± 2 vs. 2 ± 1 and PGE2, 9 ± 1 vs. 1 ± 0 pg/min. The SP release by butaprost and PGE2was similarly blocked by the EP4 receptor antagonist AH-23848 (30 μM). In anesthetized rats, the afferent renal nerve activity (ARNA) responses to butaprost 700 ± 100 and PGE2·780 ± 100%·s (area under the curve of ARNA vs. time) were unaffected by renal pelvic perfusion with AH-6809. However, 1 μM L-161,982 and 10 μM AH-23848 blocked the ARNA responses to butaprost by 94 ± 5 and 78 ± 10%, respectively, and to PGE2by 74 ± 16 and 74 ± 11%, respectively. L-161,982 also blocked the ARNA response to increasing renal pelvic pressure 10 mmHg, 85 ± 5%. In conclusion, PGE2increases renal pelvic release of SP and ARNA by activating EP4 receptors on renal sensory nerve fibers.
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| 2. |
- Kopp, UC, et al.
(författare)
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Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α2-adrenoceptors on renal sensory nerves
- 2011
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 1522-1490 .- 0363-6119. ; 300:2, s. R298-R310
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Kopp, UC, et al.
(författare)
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Dietary sodium modulates the interaction between efferent renal sympathetic nerve activity and afferent renal nerve activity: role of endothelin
- 2009
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 1522-1490 .- 0363-6119. ; 297:2, s. R337-R351
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Tidskriftsartikel (refereegranskat)abstract
- 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 PGE2and 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 PGE2release 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 PGE2release 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 PGE2and 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 PGE2release. 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.
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| 4. |
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| 5. |
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| 6. |
- Kopp, UC, et al.
(författare)
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Renal sympathetic nerve activity modulates afferent renal nerve activity by PGE2-dependent activation of alpha1- and alpha2-adrenoceptors on renal sensory nerve fibers
- 2007
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 293:4, s. R1561-R1572
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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