Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity

Kopp, Ulla C.; Jones, Susan Y.; DiBona, Gerald F.

doi:10.1152/ajpregu.90529.2008

Cited by 50 publications

(32 citation statements)

References 44 publications

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“…It has been also suggested that, in conditions of high-sodium dietary intake, activation of the afferent renal nerves contributes to the arterial baroreceptor-mediated suppression of efferent sympathetic renal nerves in the overall goal of preventing sodium retention and maintaining water and sodium homeostasis. 29,30 Therefore, renal denervation in patients with resistant hypertension and OSA might attenuate the effects of sympathoactivation additionally and independently of CPAP treatment. Whether the significant improvements in glycemic control are attributed to improved sleep apnea, because of reduced sympathetic activation, or other mechanisms remains to be determined.…”

Section: Witkowski Et Al Renal Denervation and Sleep Apnea 563mentioning

confidence: 99%

Effects of Renal Sympathetic Denervation on Blood Pressure, Sleep Apnea Course, and Glycemic Control in Patients With Resistant Hypertension and Sleep Apnea

Witkowski

Prejbisz²,

Florczak³

et al. 2011

Hypertension

429

269

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Abstract-Percutaneous renal sympathetic denervation by radiofrequency energy has been reported to reduce blood pressure (BP) by the reduction of renal sympathetic efferent and afferent signaling. We evaluated the effects of this procedure on BP and sleep apnea severity in patients with resistant hypertension and sleep apnea. We studied 10 patients with refractory hypertension and sleep apnea (7 men and 3 women; median age: 49.5 years) who underwent renal denervation and completed 3-month and 6-month follow-up evaluations, including polysomnography and selected blood chemistries, and BP measurements. Antihypertensive regimens were not changed during the 6 months of follow-up. Three and 6 months after the denervation, decreases in office systolic and diastolic BPs were observed (median: Ϫ34/Ϫ13 mm Hg for systolic and diastolic BPs at 6 months; both PϽ0.01). Significant decreases were also observed in plasma glucose concentration 2 hours after glucose administration (median: 7.0 versus 6.4 mmol/L; Pϭ0.05) and in hemoglobin A1C level (median: 6.1% versus 5.6%; PϽ0.05) at 6 months, as well as a decrease in apnea-hypopnea index at 6 months after renal denervation (median: 16.3 versus 4.5 events per hour; Pϭ0.059). In conclusion, catheter-based renal sympathetic denervation lowered BP in patients with refractory hypertension and obstructive sleep apnea, which was accompanied by improvement of sleep apnea severity. Interestingly, there are also accompanying improvements in glucose tolerance. Renal sympathetic denervation may conceivably be a potentially useful option for patients with comorbid refractory hypertension, glucose intolerance, and obstructive sleep apnea, although further studies are needed to confirm these proof-of-concept data. (Hypertension. 2011;58:559-565.)

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Section: Witkowski Et Al Renal Denervation and Sleep Apnea 563mentioning

confidence: 99%

Effects of Renal Sympathetic Denervation on Blood Pressure, Sleep Apnea Course, and Glycemic Control in Patients With Resistant Hypertension and Sleep Apnea

Witkowski

Prejbisz²,

Florczak³

et al. 2011

Hypertension

429

269

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“…Accumulating evidence indicates that sensory nerves play a key role in regulating blood pressure [1][2][3] . The transient receptor potential vanilloid type 1 (TRPV1) channel is abundantly expressed in sensory nerves [4,5] and conveys the intricate task of modulating the function of these nerves.…”

Section: Introductionmentioning

confidence: 99%

Enhanced salt sensitivity following shRNA silencing of neuronal TRPV1 in rat spinal cord

Wang

2011

Acta Pharmacol Sin

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Aim: To investigate the effects of selective knockdown of TRPV1 channels in the lower thoracic and upper lumbar segments of spinal cord, dorsal root ganglia (DRG) and mesenteric arteries on rat blood pressure responses to high salt intake. Methods: TRPV1 short-hairpin RNA (shRNA) was delivered using intrathecal injection (6 μg·kg -1 ·d -1 , for 3 d). Levels of TRPV1 and tyrosine hydroxylase expression were determined by Western blot analysis. Systolic blood pressure and mean arterial pressure (MAP) were examined using tail-cuff and direct arterial measurement, respectively. Results: In rats injected with control shRNA, high-salt diet (HS) caused higher systolic blood pressure compared with normal-salt diet (NS) (HS:149±4 mmHg; NS:126±2 mmHg, P<0.05). Intrathecal injection of TRPV1 shRNA signifi cantly increased the systolic blood pressure in both HS rats and NS rats (HS:169±3 mmHg; NS:139±2 mmHg). The increases was greater in HS rats than in NS rats (HS: 13.9%±1.8%; NS: 9.8±0.7, P<0.05). After TRPV1 shRNA treatment, TRPV1 expression in the dorsal horn and DRG of T8-L3 segments and in mesenteric arteries was knocked down to a greater extent in HS rats compared with NS rats. Blockade of α1-adrenoceptors abolished the TRPV1 shRNA-induced pressor effects. In rats injected with TRPV1 shRNA, level of tyrosine hydroxylase in mesenteric arteries was increased to a greater extent in HS rats compared with NS rats. Conclusion: Selective knockdown of TRPV1 expression in the lower thoracic and upper lumbar segments of spinal cord, DRG, and mesenteric arteries enhanced the prohypertensive effects of high salt intake, suggesting that TRPV1 channels in these sites protect against increased salt sensitivity, possibly via suppression of sympatho-excitatory responses.

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“…These rats are characterized by increased ERSNA, increased responsiveness of ERSNA to various sympathetic stimuli, and increased arterial pressure when fed a high-sodium diet. 4 There is considerable evidence for increased ERSNA contributing to hypertension. Renal denervation reduces arterial pressure in various animal models of hypertension.…”

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Impaired Interaction Between Efferent and Afferent Renal Nerve Activity in SHR Involves Increased Activation of α ₂ -Adrenoceptors

2011

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Abstract-Activation of efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), leading to decreases in ERSNA by activation of the renorenal reflexes in the overall goal of maintaining low ERSNA. The renorenal reflex responses to various stimuli are impaired in spontaneously hypertensive rats (SHR). Because renal tissue density of ␣ 2 -adrenoceptors (ARs) is increased in SHR, we examined whether the ERSNA-induced increases in ARNA are impaired in SHR and, if so, the role of ␣ 2 -ARs. The ARNA responses to increases in ERSNA were impaired in SHR, 2390Ϯ460%⅐seconds, versus in Wistar-Kyoto rats, 6620Ϯ1690%⅐seconds. Renal pelvic release of substance P was not altered by 6250 pmol/L norepinephrine (NE) in SHR but was increased by 250 pmol/L NE in Wistar-Kyoto rats, from 5.7Ϯ0.7 to 12.5Ϯ1.3 pg/min. Renal pelvic administration of the ␣ 2 -AR antagonist rauwolscine enhanced the ERSNA-induced increases in ARNA, 4170Ϯ900%⅐seconds, in SHR but not in Wistar-Kyoto rats. In the presence of rauwolscine, 250 pmol/L NE increased substance P release, from 5.2Ϯ0.3 to 11.2Ϯ0.8 pg/min, in pelvises from SHR. Because angiotensin II suppresses the activation of renal mechanosensory nerves in SHR, we examined whether losartan improved the ERSNA-induced ARNA responses. Losartan had no effect on the ARNA responses or the NE-induced increases in substance P in SHR. However, losartanϩrauwolscine resulted in further enhancement of the responsiveness of the renal sensory nerves to increases in ERSNA and NE in SHR but not in WKY. We conclude that increased activation of renal ␣ 2 -ARs and angiotensin II type 1 receptors contributes to the impaired interaction between ERSNA and ARNA in SHR. Key Words: kidney Ⅲ sensory nerves Ⅲ sympathetic nerves Ⅲ substance P Ⅲ PGE 2 Ⅲ angiotensin T he kidney has a rich supply of sympathetic nerves that innervate all parts of the nephron and the renal vasculature. 1 The kidney also has abundant afferent sensory innervation, located primarily in the renal pelvic wall. 2,3 Sympathetic efferent nerve fibers and afferent sensory nerve fibers often run separately but intertwined in the same nerve bundles in the renal pelvic wall, 2 providing anatomic support for a functional interaction between efferent renal sympathetic nerve activity (ERSNA) and afferent renal nerve activity (ARNA). In normotensive rats, activation of the renal sensory nerves leads to decreases in ERSNA and natriuresis, an inhibitory renorenal reflex response. 1 Not only do increases in ARNA decrease ERSNA but also reflex increases in ERSNA increase ARNA. 2,3 The increased ARNA will, in turn, decrease ERSNA via activation of the renorenal reflexes, a negative-feedback mechanism, to maintain low-level ERSNA.Changes in ERSNA modulate ARNA by the release of norepinephrine (NE), which activates ␣ 1 -adrenoceptors (ARs) and ␣ 2 -ARs on renal sensory nerves, leading to increases and decreases in ARNA, respectively. 2 The physiologic importance of the ERSNA-induced increases in ARNA is underlined by the interactio...

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Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity

Cited by 50 publications

References 44 publications

Effects of Renal Sympathetic Denervation on Blood Pressure, Sleep Apnea Course, and Glycemic Control in Patients With Resistant Hypertension and Sleep Apnea

Effects of Renal Sympathetic Denervation on Blood Pressure, Sleep Apnea Course, and Glycemic Control in Patients With Resistant Hypertension and Sleep Apnea

Enhanced salt sensitivity following shRNA silencing of neuronal TRPV1 in rat spinal cord

Impaired Interaction Between Efferent and Afferent Renal Nerve Activity in SHR Involves Increased Activation of α ₂ -Adrenoceptors

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Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity

Cited by 50 publications

References 44 publications

Effects of Renal Sympathetic Denervation on Blood Pressure, Sleep Apnea Course, and Glycemic Control in Patients With Resistant Hypertension and Sleep Apnea

Effects of Renal Sympathetic Denervation on Blood Pressure, Sleep Apnea Course, and Glycemic Control in Patients With Resistant Hypertension and Sleep Apnea

Enhanced salt sensitivity following shRNA silencing of neuronal TRPV1 in rat spinal cord

Impaired Interaction Between Efferent and Afferent Renal Nerve Activity in SHR Involves Increased Activation of α 2 -Adrenoceptors

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Impaired Interaction Between Efferent and Afferent Renal Nerve Activity in SHR Involves Increased Activation of α ₂ -Adrenoceptors