Activation of renal mechanosensitive neurons involves  bradykinin, protein kinase C, PGE<sub>2</sub>, and substance P

Kopp, Ulla C.; Farley, Donna M.; Cicha, Michael Z.; Smith, Lori

doi:10.1152/ajpregu.2000.278.4.r937

Cited by 36 publications

(86 citation statements)

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“…ARNA integrated over 1-second intervals was expressed as a percentage of that at baseline. 1,[5][6][7][8][9]11,12 Effects of Increasing Renal Pelvic Pressure on ARNA DRX rats (nϭ9) and sham-DRX rats (nϭ10) fed the HNa diet were studied. Renal pelvic pressure was increased by 5 and 15 mm Hg, in random order, for two 5-minute experimental periods bracketed by 10-minute control and recovery periods.…”

Section: Recording Of Pulsatile Arterial Pressure In Conscious Ratsmentioning

confidence: 99%

Dietary Sodium Loading Increases Arterial Pressure in Afferent Renal–Denervated Rats

2003

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Abstract-In rats fed high sodium diet, increasing renal pelvic pressure Ն3 mm Hg activates renal mechanosensory nerves, resulting in a renorenal reflex-induced increase in urinary sodium excretion. The low activation threshold of the renal mechanosensory nerves suggests a role for natriuretic renorenal reflexes in the regulation of arterial pressure and sodium balance. If so, interruption of the afferent renal innervation by dorsal rhizotomy (DRX) at T 9 -L 1 would impair urinary sodium excretion and/or increase arterial pressure during high dietary sodium intake. DRX and sham-DRX rats were fed either a high or a normal sodium diet for 3 weeks. Mean arterial pressure measured in conscious rats was higher in DRX than in sham-DRX rats fed a high sodium diet, 130Ϯ2 vs 100Ϯ3 mm Hg (PϽ0.01). However, mean arterial pressure was similar in DRX and sham-DRX rats fed a normal sodium diet, 115Ϯ1 and 113Ϯ1 mm Hg, respectively. Steady-state urinary sodium excretion was similar in DRX and sham-DRX rats on high (17.9Ϯ2.2 and 16.4Ϯ1.8 mmol/24 h, respectively) and normal (4.8Ϯ0.3 and 5.0Ϯ0.4 mmol/24 h, respectively) sodium diets. Studies in anesthetized rats showed a lack of an increase in afferent renal nerve activity in response to increased renal pelvic pressure and impaired prostaglandin E 2 -mediated release of substance P from the renal pelvic nerves in DRX rats fed either a high or a normal sodium diet, suggesting that DRX resulted in decreased responsiveness of peripheral renal sensory nerves. In conclusion, when the afferent limb of the renorenal reflex is interrupted, a high sodium diet results in increased arterial pressure to facilitate the natriuresis and maintenance of sodium balance. Key Words: renal nerves Ⅲ hypertension, sodium dependent Ⅲ sodium, dietary Ⅲ urine Ⅲ natriuresis I n the kidney, the majority of renal sensory nerves containing substance P are located in the renal pelvic wall. 1,2 The afferent renal nerves project to the ipsilateral dorsal root ganglia at the T 6 -L 2 level, with the majority of cell bodies of the afferent renal nerves being at the T 9 -L 1 level. 3,4 The renal sensory nerves are activated by increases in renal pelvic pressure within the physiologic range. 5 The increase in afferent renal nerve activity (ARNA) produced by the increased renal pelvic pressure leads to a reflex decrease in efferent renal sympathetic nerve activity (ERSNA) and diuresis and natriuresis, ie, a renorenal reflex response. 6 Increasing renal pelvic pressure elicits a series of events eventually leading to increases in ARNA. Among the various mechanisms activated by increased renal pelvic pressure is stimulation of bradykinin-2 receptors that activate protein kinase C, which leads to activation of cyclooxygenase-2 and increased prostaglandin E 2 (PGE 2 ) synthesis. 7-9 PGE 2 activates cAMP, which leads to a calcium-dependent release of substance P from the renal sensory nerves. 10,11 Substance P increases ARNA by stimulating neurokinin-1 receptors. 12 The responsiveness of renal sensory nerves is modulated by...

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Section: Recording Of Pulsatile Arterial Pressure In Conscious Ratsmentioning

confidence: 99%

Dietary Sodium Loading Increases Arterial Pressure in Afferent Renal–Denervated Rats

2003

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“…The ERSNA-induced increase in ARNA would exert a powerful negative feedback control of ERSNA via activation of the renorenal reflexes in the overall goal of maintaining low ERSNA to prevent sodium retention. The functional importance of the renorenal reflex is underlined by the low activation threshold, ϳ3 mmHg in renal pelvic pressure (21), and its abolition resulting in salt-sensitive hypertension (20).Among the mechanisms involved in the activation of the renal mechanosensory nerves produced by stretching the renal pelvic wall are induction of cyclooxygenase-2 (COX-2) leading to increased renal pelvic synthesis of PGE 2 (23,24,27). PGE 2 increases the release of substance P via activation of the cAMP-PKA signal transduction pathway.…”

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confidence: 99%

“…Among the mechanisms involved in the activation of the renal mechanosensory nerves produced by stretching the renal pelvic wall are induction of cyclooxygenase-2 (COX-2) leading to increased renal pelvic synthesis of PGE 2 (23,24,27). PGE 2 increases the release of substance P via activation of the cAMP-PKA signal transduction pathway.…”

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“…In this way, we could also study whether the effects produced by reflex ERSNA involved activation of pre-or postsynaptic adrenoceptors. PGE 2 plays an important role in the activation of renal mechanosensory receptors (23,24,26,27) and sensitizes the sensory receptors to numerous stimuli (e.g., 11,16,37,40). Therefore, we examined whether PGE 2 was also involved in the norepinephrine-induced activation of renal pelvic sensory nerves.…”

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

Kopp

Cicha²,

Smith³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Kopp UC, Cicha MZ, Smith LA, Mulder J, Hö kfelt T. Renal sympathetic nerve activity modulates afferent renal nerve activity by PGE 2-dependent activation of ␣1-and ␣2-adrenoceptors on renal sensory nerve fibers. Am J Physiol Regul Integr Comp Physiol 293: R1561-R1572, 2007. First published August 15, 2007; doi:10.1152/ajpregu.00485.2007.-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 ␣-adrenoceptors on the renal sensory nerves, we examined the effects of renal pelvic administration of the ␣ 1-and ␣2-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 Ϯ 900 and 4,870 Ϯ 670% ⅐ s (area under the curve ARNA vs. time). Renal pelvic perfusion with norepinephrine increased ARNA 1,870 Ϯ 210% ⅐ 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 Ϯ 1 to 16 Ϯ 1 pg/min, and PGE 2 release, from 77 Ϯ 11 to 161 Ϯ 23 pg/min, suggesting a role for PGE 2 in the norepinephrineinduced activation of renal sensory nerves. Prazosin and indomethacin reduced and rauwolscine enhanced the norepinephrine-induced increases in substance P and PGE 2. 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 ␣ 1-and ␣2-adrenoceptors, respectively, on the renal pelvic sensory nerve fibers. Norepinephrine-induced activation of the sensory nerves is dependent on renal pelvic synthesis/release of PGE 2. substance P; EP4 receptor; pelvis; prazosin; rauwolscine THERE IS CONSIDERABLE EVIDENCE for increased sympathetic nerve activation to further stimulate sensory nerve fibers following tissue injury (15). Studies on efferent renal sympathetic nerve activity (ERSNA) and afferent renal nerve activity (ARNA) suggest that such an interaction is not restricted to conditions of tissue injury but is an important mechanism regulating ERSNA during physiological conditions (30). The kidney has a rich supply of sympathetic nerves, which innervate all parts of the vasculature and the nephron (2). In contrast, the majority of the sensory nerve fibers are localized to the renal pelvic wall (25,26,32). There is anatomical support for an interaction between ERSNA and ARNA, as shown by the close relationship between unmyelinated sympathetic nerve fibers and myelinated afferent nerve fibers in renal tissue...

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“…1,2,6,7,9,10 In brief, after anesthesia, renal pelvises dissected from the kidneys were placed in wells containing 400 L of HEPES buffer (pH 7.4), 37°C, containing indomethacin (0.14 mmol/L) to minimize the influence of endogenous PGE 2 on substance P release. Each well contained the pelvic wall from 1 kidney.…”

Section: Substance P Release From An Isolated Renal Pelvic Wall Prepamentioning

confidence: 99%

Activation of Endothelin-A Receptors Contributes to Angiotensin-Induced Suppression of Renal Sensory Nerve Activation

2007

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Abstract-Activation of renal mechanosensory nerves is enhanced by a high-sodium diet and suppressed by a low-sodium diet. Angiotensin (Ang) II and endothelin (ET)-1 each contributes to the impaired responsiveness of renal mechanosensory nerves in a low-sodium diet. We examined whether stimulation of ETA receptors (Rs) contributes to Ang II-induced suppression of the responsiveness of renal mechanosensory nerves. In anesthetized rats fed a low-sodium diet, renal pelvic administration of the Ang type I receptor (AT1-R) antagonist losartan enhanced the afferent renal nerve activity (ARNA) response to increasing renal pelvic pressure 7.5 mm Hg from 7Ϯ2% to 15Ϯ2% and the prostaglandin (PG) E 2 -mediated substance P release from 0Ϯ1 to 8Ϯ1 pg/min. Adding the ETA-R antagonist BQ123 to the renal pelvic perfusate containing losartan did not produce any further enhancement of the ARNA response or PGE 2 -mediated release of substance P (17Ϯ3% and 8Ϯ1 pg/min). Likewise, renal pelvic administration of BQ123 and BQ123ϩlosartan resulted in similar enhancements of the ARNA responses to increased renal pelvic pressure and PGE 2 -mediated substance P release. In high-sodium-diet rats, pelvic administration of Ang II reduced the ARNA response to increased renal pelvic pressure from 27Ϯ4% to 8Ϯ3% and the PGE 2 -mediated substance P release from 9Ϯ0 to 1Ϯ1 pg/min. Adding BQ123 to the renal pelvic perfusate containing Ang II restored the increases in ARNA and the PGE 2 -mediated substance P release toward control (27Ϯ6% and 7Ϯ1 pg/min). In conclusion, stimulation of ETA-R plays an important contributory role to the Ang II-mediated suppression of the activation of renal mechanosensory nerves in conditions of low-sodium diet. Key Words: ETA-receptors Ⅲ AT1-receptors Ⅲ afferent renal nerves Ⅲ PGE 2 Ⅲ substance P Ⅲ BQ123 Ⅲ losartan T he majority of the afferent renal nerves are located in the renal pelvic wall. 1-3 Activation of these nerves by increases in renal pelvic pressure results in increases in afferent renal nerve activity (ARNA) leading to reflex decreases in efferent renal sympathetic nerve activity and diuresis and natriuresis, that is, a renorenal reflex response. 4 Among the various mechanisms activated by stretching the renal pelvic wall is induction of cyclooxygenase-2 resulting in increased renal pelvic synthesis of PGE 2 . 5,6 PGE 2 leads to activation of the cAMP-protein kinase A transduction pathway and a release of the neuropeptide substance P, which activates the afferent renal nerves by stimulating neurokinin-1 receptors in the renal pelvic area. 1,7,8 The responsiveness of the afferent renal nerves is enhanced by high-sodium diet and suppressed by low-sodium diet because of an interaction between prostaglandin (PG) E 2 (PGE 2 ) and angiotensin (Ang) II at the peripheral renal sensory nerve endings. 7,9,10 In conditions of high-sodium diet, characterized by low endogenous Ang II, 11 there is little or no inhibition of the PGE 2 -mediated activation of adenylyl cyclase. Conversely, in conditions of low-sodium diet, ...

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Activation of renal mechanosensitive neurons involves bradykinin, protein kinase C, PGE₂, and substance P

Cited by 36 publications

References 47 publications

Dietary Sodium Loading Increases Arterial Pressure in Afferent Renal–Denervated Rats

Dietary Sodium Loading Increases Arterial Pressure in Afferent Renal–Denervated Rats

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

Activation of Endothelin-A Receptors Contributes to Angiotensin-Induced Suppression of Renal Sensory Nerve Activation

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Activation of renal mechanosensitive neurons involves bradykinin, protein kinase C, PGE2, and substance P

Cited by 36 publications

References 47 publications

Dietary Sodium Loading Increases Arterial Pressure in Afferent Renal–Denervated Rats

Dietary Sodium Loading Increases Arterial Pressure in Afferent Renal–Denervated Rats

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

Activation of Endothelin-A Receptors Contributes to Angiotensin-Induced Suppression of Renal Sensory Nerve Activation

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Activation of renal mechanosensitive neurons involves bradykinin, protein kinase C, PGE₂, and substance P

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