Abstract MP21: Circadian Cycle Exaggerates Sympathoexcitatory Responses To Activation Of Chemosensitive Renal Sensory Nerves

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Leon J DeLalio ◽  
Sean D Stocker
Keyword(s):  
Sympathetic Nerve Activity ◽  
Sensory Nerve ◽  
Sensory Nerves ◽  
Circadian Cycle ◽  
Nerve Activity ◽  
Arterial Infusion ◽  
Arterial Blood ◽  
Inactive Phase ◽  
The Impact ◽  
Circadian Patterns

Renal sensory nerves contribute to hypertension and renal dysfunction in chronic kidney disease. Selective chemokines (e.g., bradykinin or capsaicin) activate renal sensory nerves and produce reflexive efferent sympathetic nerve activity (SNA) and arterial blood pressure (ABP) responses. SNA, ABP, and renal function exhibit circadian patterns; yet the impact of circadian cycle on chemosensitive responses is unknown. We hypothesized that SNA and hemodynamic responses would be greater during the active phrase or nighttime versus the inactive phase or daytime. In Inactin anesthetized rats, simultaneous renal and splanchnic SNA and ABP were measured during intrarenal arterial infusion of capsaicin or bradykinin (0.1 μM - 30.0 μM; 50 μl over 15 s) at nighttime (N; 20:00-04:00; n= 12M, 10F) versus daytime (D; 09:00-16:00; n= 8M, 8F). Baseline mean ABP was significantly elevated during nighttime (N: 104±2 mmHg; D: 97±2 mmHg, p=0.04). Intrarenal capsaicin infusion produced concentration-dependent increases in renal and splanchnic SNA. Renal SNA increased more at nighttime versus daytime at 10 μM (N: 723±136 vs D: 409±79 %; p=0.03) and 30 μM (N: 826±181 vs D: 509±80 %; p=0.03). Similarly, splanchnic SNA was greater during nighttime versus daytime at 10 μM (N: 501±117 vs D: 204±53 %, p=0.03) and 30 μM (N: 537±101 vs D: 295±68 %; p=0.03). However, ABP responses were similar between nighttime versus daytime (30uM: 7±1 vs 6±1 mmHg, respectively). Intrarenal infusion of bradykinin produced concentration-dependent increases in renal and splanchnic SNA. Renal SNA increased more at nighttime versus daytime at 10 μM (N: 1773±216 vs D: 1249±112 %; p=0.01) and 30 μM (N: 2605±263 vs D: 1783±163 %; p=0.001). Similarly, splanchnic SNA was exaggerated at nighttime versus daytime at 0.1 μM (N: 163±65 vs D: 0±0 %; p=0.02), 1.0 μM (N: 566±114 vs D: 184±52 %; p=0.005), 10 μM (N: 1110±193 vs D: 583±87 %; p=0.006) and 30 μM (N: 2008±193 vs D: 1044±162 %; p<0.001). ABP response were similar between nighttime versus daytime at 30 μM (10±2 vs 6±1 mmHg, respectively). Circadian cycle exaggerates sympathoexcitatory responses produced by chemosensitive renal sensory nerve activation.

Abstract MP48: Crispr/cas9 Trpv1 Deletion In Rats Does Not Impair Mechano- And Chemo-sensory Renal Afferent Nerve Responses

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Leon J DeLalio ◽  
Sean D Stocker
Keyword(s):  
Kidney Disease ◽  
Transient Receptor Potential ◽  
Sensory Nerve ◽  
Afferent Nerve ◽  
Sensory Nerves ◽  
Transient Receptor Potential Vanilloid ◽  
Wild Type ◽  
Trpv1 Channels ◽  
Arterial Blood ◽  
The Impact

Elevated renal afferent nerve activity (ARNA) or dysfunctional renal reflexes contributes to hypertension and chronic kidney disease. The transient receptor potential vanilloid type-1 (TRPV1) channel is expressed in renal sensory nerves, and intrarenal administration of the TRPV1 agonist capsaicin increases ARNA. Nonselective denervation of renal sensory nerves using high-concentration capsaicin reduces arterial blood pressure (ABP) in experimental models of hypertension. However, the role of TRPV1 channels in ARNA responses to chemo- and mechano-sensitive stimuli has not been directly tested. To test this hypothesis, we generated a novel TRPV1 rat knockout model (TRPV1 -/- ) using CRISPR/CAS9 to delete exon 3 . ARNA multifiber recordings were performed in male and female TRPV1 -/- and wild-type littermates (250-400g) after decerebration or Inactin anesthesia (data combined). Wild-type and TRPV1 -/- rats had no significant differences in baseline mean ABP (126±4 mmHg vs 138±5 mmHg, respectively; n=8-10) or heart rate (451±25 bpm vs 432±24 bpm, respectively; n=8-10). Baseline ARNA was not different between wild-type and TRPV1 -/- rats (16±3 Hz vs 28±6 Hz, respectively; n=8-10). Intrarenal artery infusion of the TRPV1 agonist capsaicin (0.1-10μM, 50μL per 15s) significantly increased ipsilateral ARNA in wild-type but not TRPV1 -/- rats (Δ discharge with 10μM: 65±3 Hz vs 6±1 Hz, respectively; n=5-7). As a second chemosensitive stimulus, intrarenal artery infusion of bradykinin (0.1-10μM, 50μL per 15s) produced similar increases in ipsilateral ARNA between wild-type and TRPV1 -/- rats (Δ discharge with 10μM: 52±6 Hz vs 73±18 Hz, respectively; n=5-6). Finally, elevated renal pelvic pressures (0-20mmHg; 30s) significantly increased ipsilateral ARNA in both wild-type and TRPV1 -/- rats; however, the ARNA response was significantly greater in TRPV1 -/- versus wild-type rats (Δ discharge with 20mmHg: 47±14 Hz versus 18±6 Hz, respectively; n=5-8). In conclusion, mechanosensitive and chemosensitive ARNA responses remain intact in TRPV1 -/- rats. The mechanisms responsible for renal sensory nerve activation remain unidentified and the impact of TRPV1 deletion in rat models of hypertension and kidney disease remains to be tested.

Abstract MP45: Deletion Of The Transient Receptor Vanilloid-1 (TRPV1) Channel In Rats Attenuates 2 Kidney 1 Clip Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Sean D Stocker ◽  
Leon J DeLalio
Keyword(s):  
Heart Rate ◽  
Renovascular Hypertension ◽  
Sensory Nerve ◽  
Experimental Models ◽  
Sensory Nerves ◽  
Male Rats ◽  
Wild Type ◽  
Renal Nerve ◽  
Trpv1 Channels ◽  
Arterial Blood

Renal denervation lowers arterial blood pressure (ABP) in both clinical populations and multiple experimental models of hypertension. This therapeutic effect is partly attributed to the removal of overactive renal sensory nerves that increase sympathetic efferent activity and ABP. Renal sensory nerves highly express TRPV1 channels, and administration of the TRPV1 agonist capsaicin increases renal sensory nerve activity. However, the extent by which TRPV1 channels directly contribute to renal nerve dependent models of hypertension has not been tested. To test this hypothesis, we generated a novel TRPV1 -/- rat using CRISPR/Cas9 and deletion of exon 3. Male and female TRPV1 -/- and wild-type littermates (8-12 weeks) were instrumented with telemetry. At 2 weeks later, renovascular hypertension via renal stenosis was produced by placement of a PTFE cuff (0.16 x 0.22 inches, 1mm long) around the right renal artery. Male TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (99±2 vs 98±3 mmHg, respectively; n=7-9) or heart rate (390±7 vs 400±8 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, mean ABP was significantly lower at Day 28 in male TRPV1 -/- versus wild-type rats (125±8 vs 155±2 mmHg, respectively: P<0.01). Ganglionic blockade with chlorisondamine (2.5mg/kg, sc) at Day 28 produced a smaller fall in mean ABP of male TRPV1 -/- versus wild-type rats (-53±4 vs -86±3 mmHg, respectively; P<0.001). On the other hand, female TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (102±2 vs 104±1 mmHg, respectively; n=6-9) or heart rate (419±8 vs 410±7 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, there were no differences at Day 28 between female TRPV1 -/- versus wild-type rats (117±8 vs 122±6 mmHg, respectively). Moreover, the increase in mean ABP was smaller in females versus males. The ganglionic blocker chlorisondamine produced similar depressor responses in female TRPV1 -/- versus wild-type rats (-64±7 vs -65±7 mmHg, respectively). These findings illustrate a sex difference in renovascular hypertension in rats, but importantly indicate that TRPV1 channels contribute to the established phase of renovascular hypertension in male rats.

Modulation of sympathetic nerve activity during posthandgrip muscle ischemia in humans

1994 ◽  
Vol 266 (1) ◽  
pp. H79-H83 ◽  
Author(s):  
C. A. Ray ◽  
N. H. Secher ◽  
A. L. Mark
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Sensory Nerve ◽  
Vascular Occlusion ◽  
Voluntary Contraction ◽  
Central Command ◽  
Isometric Handgrip ◽  
Nerve Activity ◽  
Muscle Ischemia

To evaluate modulation of muscle sympathetic nerve activity (MSNA) during posthandgrip muscle ischemia (PHGMI), subjects performed 2 min of isometric handgrip at 33% of maximal voluntary contraction (MVC) followed by 2 min of PHGMI produced by forearm vascular occlusion. The response to PHGMI was studied in the absence and again during the addition of contralateral rhythmic handgrip (RHG; 40 times/min) at 15% (n = 6) and 30% (n = 10) MVC during the second minute of the PHGMI. Additionally, to isolate the effect of central command, response to PHGMI was studied during attempted RHG after sensory nerve blockade (n = 5). RHG for 2 min at 15 and 30% MVC and attempted RHG for 2 min did not increase MSNA. Isometric handgrip elicited an 130 +/- 48% increase in MSNA (P < 0.05), which was maintained during PHGMI. RHG at 15 and 30% MVC elicited an attenuation of MSNA (-10 +/- 7% and -14 +/- 6%, respectively) when performed during the second minute of PHGMI (P < 0.05). In contrast, attempted RHG did not significantly affect MSNA during PHGMI. The findings demonstrate modulation of MSNA during activation of the muscle metaboreflex. The attenuation of metaboreceptor-mediated increases in MSNA appear to be the result of mechanosensitive muscle afferents and not central command.

scholarly journals Spontaneous bursts of muscle sympathetic nerve activity decrease leg vascular conductance in resting humans

2013 ◽  
Vol 304 (5) ◽  
pp. H759-H766 ◽  
Author(s):  
Seth T. Fairfax ◽  
Jaume Padilla ◽  
Lauro C. Vianna ◽  
Michael J. Davis ◽  
Paul J. Fadel
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Burst Size ◽  
Muscle Sympathetic Nerve Activity ◽  
Common Femoral Artery ◽  
Vascular Conductance ◽  
Nerve Activity ◽  
Arterial Blood

Previous studies in humans attempting to assess sympathetic vascular transduction have related large reflex-mediated increases in muscle sympathetic nerve activity (MSNA) to associated changes in limb vascular resistance. However, such procedures do not provide insight into the ability of MSNA to dynamically control vascular tone on a beat-by-beat basis. Thus we examined the influence of spontaneous MSNA bursts on leg vascular conductance (LVC) and how variations in MSNA burst pattern (single vs. multiple bursts) and burst size may affect the magnitude of the LVC response. In 11 young men, arterial blood pressure, common femoral artery blood flow, and MSNA were continuously recorded during 20 min of supine rest. Signal averaging was used to characterize percent changes in LVC for 15 cardiac cycles following heartbeats associated with and without MSNA bursts. LVC significantly decreased following MSNA bursts, reaching a nadir during the 6th cardiac cycle (single bursts, −2.9 ± 1.1%; and multiple bursts, −11.0 ± 1.4%; both, P < 0.001). Individual MSNA burst amplitudes and the total amplitude of consecutive bursts were related to the magnitude of peak decreases in LVC. In contrast, cardiac cycles without MSNA bursts were associated with a significant increase in LVC (+3.1 ± 0.5%; P < 0.001). Total vascular conductance decreased in parallel with LVC also reaching a nadir around the peak rise in arterial blood pressure following an MSNA burst. Collectively, these data are the first to assess beat-by-beat sympathetic vascular transduction in resting humans, demonstrating robust and dynamic decreases in LVC following MSNA bursts, an effect that was absent for cardiac cycles without MSNA bursts.

The impact of 6 months of exercise-based cardiac rehabilitation on sympathetic neural recruitment during apneic stress

2021 ◽  
Author(s):  
Andrew D'Souza ◽  
Mark B. Badrov ◽  
Katelyn N. Wood ◽  
Sophie Lalande ◽  
Neville Gordon Suskin ◽  
...  
Keyword(s):  
Cardiac Rehabilitation ◽  
Sympathetic Activity ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Firing Frequency ◽  
Sympathetic Activation ◽  
Nerve Activity ◽  
Sympathetic Nervous ◽  
Discharge Patterns ◽  
The Impact

The current study evaluated the hypothesis that six months of exercise-based cardiac rehabilitation (CR) would improve sympathetic neural recruitment in patients with ischemic heart disease (IHD). Microneurography was used to evaluate action potential (AP) discharge patterns within bursts of muscle sympathetic nerve activity (MSNA), in eleven patients with IHD (1 female; 61±9 years) pre- (Pre-CR) and post- six months of aerobic and resistance training-based CR (Post-CR). Measures were made at baseline and during maximal voluntary end-inspiratory (EI-APN) and end-expiratory apneas (EE-APN). Data were analyzed during 1-minute of baseline and the second half of apneas. At baseline, overall sympathetic activity was less Post-CR (all P<0.01). During EI-APN, AP recruitment was not observed Pre-CR (all P>0.05) but increases in both within-burst AP firing frequency (∆Pre-CR: 2±3 AP spikes/burst vs. ∆Post-CR: 4±3 AP spikes/burst; P=0.02) and AP cluster recruitment (∆Pre-CR: -1±2 vs. ∆Post-CR: 2±2; P<0.01) were observed in Post-CR tests. In contrast, during EE-APN, AP firing frequency was not different Post-CR compared to Pre-CR tests (∆Pre-CR: 269±202 spikes/min vs. ∆Post-CR: 232±225 spikes/min; P=0.54), and CR did not modify the recruitment of new AP clusters (∆Pre-CR: -1±3 vs. ∆Post-CR: 0±1; P=0.39), or within-burst firing frequency (∆Pre-CR: 3±3 AP spikes/burst vs. ∆Post-CR: 2±2 AP spikes/burst; P=0.21). These data indicate that CR improves some of the sympathetic nervous system dysregulation associated with cardiovascular disease, primarily via a reduction in resting sympathetic activation. However, the benefits of CR on sympathetic neural recruitment may depend upon the magnitude of initial impairment.

Abstract 081: Renal Sensory Nerves Increase Blood Pressure and Sympathetic Nerve Activity in 2-Kidney 1-Clip Hypertensive Mice

Hypertension ◽  
2018 ◽  
Vol 72 (Suppl_1) ◽  
Author(s):  
Jason Ong ◽  
Alan F Sved ◽  
Roderick J Tan ◽  
Brittney M Rush ◽  
Marcelo D Carattino ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Sensory Nerves ◽  
Increase Blood Pressure ◽  
Nerve Activity

Interactions between ANP and ANG II in regulating blood pressure and sympathetic outflow

1991 ◽  
Vol 260 (6) ◽  
pp. R1145-R1151 ◽  
Author(s):  
M. K. Steele ◽  
D. G. Gardner ◽  
P. L. Xie ◽  
H. D. Schultz
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve Activity ◽  
Ang Ii ◽  
Contrast Injection ◽  
Synthesis Inhibitor ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Arterial Blood ◽  
Pressor Responses ◽  
Renal Sympathetic

In anesthetized rats with sinoaortic denervation, intracerebroventricular (icv) injection of atrial natriuretic peptide (ANP) resulted in decreased mean arterial blood pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) (depressor effects), whereas icv angiotensin II (ANG II) produced increases in these variables (pressor effects). The depressor effects of ANP were slower in onset and longer in duration than the pressor effects of ANG II. Intracerebroventricular injection of the ANG II-receptor blocker sarthran or the ANG II-synthesis inhibitor captopril resulted in a significant reduction in MAP; HR and RSNA were not affected. Both sarthran and captopril abolished the depressor responses to icv ANP. In contrast, injection of an anti-rat ANP antibody, which blocked the depressor effects of icv ANP, did not by itself modify MAP, HR, or RSNA, nor did the antibody affect the pressor responses to icv ANG II. These data suggest that, in this animal model, the depressor effects of icv ANP are mediated by the inhibition of brain ANG II-dependent neural activity. These results also demonstrate that, in this preparation, the endogenous ANG II system actively contributes to the maintenance of basal MAP, whereas the central ANP system, at least in regions accessible to the antirat ANP antibody, plays little role in this maintenance.

Cardiopulmonary baroreceptor control of muscle sympathetic nerve activity in heat-stressed humans

1999 ◽  
Vol 277 (6) ◽  
pp. H2348-H2352 ◽  
Author(s):  
C. G. Crandall ◽  
R. A. Etzel ◽  
D. B. Farr
Keyword(s):  
Blood Pressure ◽  
Heat Stress ◽  
Arterial Blood Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Venous Pressure ◽  
Whole Body ◽  
Nerve Activity ◽  
Arterial Blood

Whole body heating decreases central venous pressure (CVP) while increasing muscle sympathetic nerve activity (MSNA). In normothermia, similar decreases in CVP elevate MSNA, presumably via cardiopulmonary baroreceptor unloading. The purpose of this project was to identify whether increases in MSNA during whole body heating could be attributed to cardiopulmonary baroreceptor unloading coincident with the thermal challenge. Seven subjects were exposed to whole body heating while sublingual temperature, skin blood flow, heart rate, arterial blood pressure, and MSNA were monitored. During the heat stress, 15 ml/kg warmed saline was infused intravenously over 7–10 min to increase CVP and load the cardiopulmonary baroreceptors. We reported previously that this amount of saline was sufficient to return CVP to pre-heat stress levels. Whole body heating increased MSNA from 25 ± 3 to 39 ± 3 bursts/min ( P < 0.05). Central blood volume expansion via rapid saline infusion did not significantly decrease MSNA (44 ± 4 bursts/min, P > 0.05 relative to heat stress period) and did not alter mean arterial blood pressure (MAP) or pulse pressure. To identify whether arterial baroreceptor loading decreases MSNA during heat stress, in a separate protocol MAP was elevated via steady-state infusion of phenylephrine during whole body heating. Increasing MAP from 82 ± 3 to 93 ± 4 mmHg ( P < 0.05) caused MSNA to decrease from 36 ± 3 to 15 ± 4 bursts/min ( P < 0.05). These data suggest that cardiopulmonary baroreceptor unloading during passive heating is not the primary mechanism resulting in elevations in MSNA. Moreover, arterial baroreceptors remain capable of modulating MSNA during heat stress.

Arterial pressure and muscle sympathetic nerve activity are increased after two hours of sustained but not cyclic hypoxia in healthy humans

2005 ◽  
Vol 98 (1) ◽  
pp. 343-349 ◽  
Author(s):  
Renaud Tamisier ◽  
Amit Anand ◽  
Luz M. Nieto ◽  
David Cunnington ◽  
J. Woodrow Weiss
Keyword(s):  
Blood Pressure ◽  
Arterial Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Activity ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Arterial Oxygen ◽  
Nerve Activity ◽  
Arterial Blood ◽  
Sustained Hypoxia

Sustained and episodic hypoxic exposures lead, by two different mechanisms, to an increase in ventilation after the exposure is terminated. Our aim was to investigate whether the pattern of hypoxia, cyclic or sustained, influences sympathetic activity and hemodynamics in the postexposure period. We measured sympathetic activity (peroneal microneurography), hemodynamics [plethysmographic forearm blood flow (FBF), arterial pressure, heart rate], and peripheral chemosensitivity in normal volunteers on two occasions during and after 2 h of either exposure. By design, mean arterial oxygen saturation was lower during sustained relative to cyclic hypoxia. Baseline to recovery muscle sympathetic nerve activity and blood pressure went from 15.7 ± 1.2 to 22.6 ± 1.9 bursts/min ( P < 0.01) and from 85.6 ± 3.2 to 96.1 ± 3.3 mmHg ( P < 0.05) after sustained hypoxia, respectively, but did not exhibit significant change from 13.6 ± 1.5 to 17.3 ± 2.5 bursts/min and 84.9 ± 2.8 to 89.8 ± 2.5 mmHg after cyclic hypoxia. A significant increase in FBF occurred after sustained, but not cyclic, hypoxia, from 2.3 ± 0.2 to 3.29 ± 0.4 and from 2.2 ± 0.1 to 3.1 ± 0.5 ml·min−1·100 g of tissue−1, respectively. Neither exposure altered the ventilatory response to progressive isocapnic hypoxia. Two hours of sustained hypoxia increased not only muscle sympathetic nerve activity but also arterial blood pressure. In contrast, cyclic hypoxia produced slight but not significant changes in hemodynamics and sympathetic activity. These findings suggest the cardiovascular response to acute hypoxia may depend on the intensity, rather than the pattern, of the hypoxic exposure.

Effect of dynamic exercise on renal sympathetic nerve activity in conscious rabbits

1993 ◽  
Vol 74 (5) ◽  
pp. 2099-2104 ◽  
Author(s):  
K. P. O'Hagan ◽  
L. B. Bell ◽  
S. W. Mittelstadt ◽  
P. S. Clifford
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Treadmill Exercise ◽  
Dynamic Exercise ◽  
Nerve Activity ◽  
Renal Sympathetic Nerve Activity ◽  
Renal Sympathetic Nerve ◽  
Arterial Blood ◽  
Conscious Rabbits ◽  
Renal Sympathetic

Renal sympathetic nerve activity (RSNA) increases abruptly at the onset of treadmill exercise in conscious rabbits. This study investigated whether the rise in RSNA is related to the intensity of the exercise and whether an elevated level of RSNA is maintained during submaximal exercise. RSNA, arterial blood pressure (BP), and heart rate (HR) were recorded in 10 New Zealand White rabbits during two treadmill exercise protocols at 0% grade: 7 m/min for 5 min and 12 m/min for 2 min. Peak levels of RSNA were observed in the first 10 s of exercise at 7 and 12 m/min. Through 2 min of exercise, the rise in RSNA was greater (P < 0.05) at 12 m/min (delta 83 +/- 22%) compared with 7 m/min (delta 49 +/- 8%). At 7 m/min, HR and BP reached steady-state levels during the 2nd min of exercise. RSNA remained elevated at delta 43 +/- 10 to delta 54 +/- 13% over resting levels as exercise continued from the 2nd through the 5th min of exercise (P < 0.05). These data demonstrate that the RSNA response to exercise is intensity related and suggest that RSNA remains elevated and thus may contribute to the control of renal blood flow during submaximal dynamic exercise.

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