The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature

Alawi, Khadija M.; Aubdool, Aisah A.; Liang, Lijun; Wilde, Elena; Vepa, Abhinav; Psefteli, Paraskevi-Maria; Brain, Susan D.; Keeble, Julie

doi:10.1096/fj.15-272526

Cited by 55 publications

(54 citation statements)

References 59 publications

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“…For this, a ventral incision was made on the abdominal wall and irrigated with sterile saline (0.9% saline; sodium chloride, pyrogen free) to facilitate the insertion of the radiotelemetry transmitter. The outer wound was closed with absorbable sutures as above 30. All mice were singly housed and following a 10‐day recovery period, either the central blood pressure and heart rate, or temperature were recorded continuously at 1‐ to 10‐minute scheduled intervals.…”

Section: Methodsmentioning

confidence: 99%

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Tail‐Cuff Technique and Its Influence on Central Blood Pressure in the Mouse

Wilde

Aubdool

Thakore

et al. 2017

JAHA

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BackgroundReliable measurement of blood pressure in conscious mice is essential in cardiovascular research. Telemetry, the “gold‐standard” technique, is invasive and expensive and therefore tail‐cuff, a noninvasive alternative, is widely used. However, tail‐cuff requires handling and restraint during measurement, which may cause stress affecting blood pressure and undermining reliability of the results.Methods and ResultsC57Bl/6J mice were implanted with radio‐telemetry probes to investigate the effects of the steps of the tail‐cuff technique on central blood pressure, heart rate, and temperature. This included comparison of handling techniques, operator's sex, habituation, and influence of hypertension induced by angiotensin II. Direct comparison of measurements obtained by telemetry and tail‐cuff were made in the same mouse. The results revealed significant increases in central blood pressure, heart rate, and core body temperature from baseline following handling interventions without significant difference among the different handling technique, habituation, or sex of the investigator. Restraint induced the largest and sustained increase in cardiovascular parameters and temperature. The tail‐cuff readings significantly underestimated those from simultaneous telemetry recordings; however, “nonsimultaneous” telemetry, obtained in undisturbed mice, were similar to tail‐cuff readings obtained in undisturbed mice on the same day.ConclusionsThis study reveals that the tail‐cuff technique underestimates the core blood pressure changes that occur simultaneously during the restraint and measurement phases. However, the measurements between the 2 techniques are similar when tail‐cuff readings are compared with telemetry readings in the nondisturbed mice. The differences between the simultaneous recordings by the 2 techniques should be recognized by researchers.

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Section: Methodsmentioning

confidence: 99%

“…The outer wound was closed with absorbable sutures as above. 30 All mice were singly housed and following a 10-day recovery period, either the central blood pressure and heart rate, or temperature were recorded continuously at 1-to 10-minute scheduled intervals.…”

Section: Surgical Procedures For Implantation Of Telemetry Probesmentioning

confidence: 99%

Tail‐Cuff Technique and Its Influence on Central Blood Pressure in the Mouse

Wilde

Aubdool

Thakore

et al. 2017

JAHA

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“…administration of AMG7905 does not cause hypothermia in Trpv1 −/− mice, while causing pronounced hypothermia in wild‐type mice. For comparison, the on‐target nature of the hyperthermic effect has been demonstrated using Trpv1 −/− mice for several TRPV1 antagonists, viz., AMG0347, AMG 517 and AMG9810 . In addition, AMG 517 has also been shown to prevent ketamine‐induced hypothermia in mice by acting, at least partially, on TRPV1 channels …”

Section: Discussionmentioning

confidence: 99%

“…Almost immediately, several of them were reported to cause hyperthermia in laboratory animals and later in humans . This hyperthermia was shown to be an on‐target side effect, ie to occur through the TRPV1 channel . It appeared that TRPV1 antagonists cause hyperthermia by blocking the tonic suppression of the autonomic cold defences: thermogenesis and skin vasoconstriction .…”

Section: Introductionmentioning

confidence: 99%

TRPV1 antagonists that cause hypothermia, instead of hyperthermia, in rodents: Compounds’ pharmacological profiles, in vivo targets, thermoeffectors recruited and implications for drug development

et al. 2018

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AimThermoregulatory side effects hinder the development of transient receptor potential vanilloid‐1 (TRPV1) antagonists as new painkillers. While many antagonists cause hyperthermia, a well‐studied effect, some cause hypothermia. The mechanisms of this hypothermia are unknown and were studied herein.MethodsTwo hypothermia‐inducing TRPV1 antagonists, the newly synthesized A‐1165901 and the known AMG7905, were used in physiological experiments in rats and mice. Their pharmacological profiles against rat TRPV1 were studied in vitro.ResultsAdministered peripherally, A‐1165901 caused hypothermia in rats by either triggering tail‐skin vasodilation (at thermoneutrality) or inhibiting thermogenesis (in the cold). A‐1165901‐induced hypothermia did not occur in rats with desensitized (by an intraperitoneal dose of the TRPV1 agonist resiniferatoxin) sensory abdominal nerves. The hypothermic responses to A‐1165901 and AMG7905 (administered intragastrically or intraperitoneally) were absent in Trpv1 −/− mice, even though both compounds evoked pronounced hypothermia in Trpv1 +/+ mice. In vitro, both A‐1165901 and AMG7905 potently potentiated TRPV1 activation by protons, while potently blocking channel activation by capsaicin.Conclusion TRPV1 antagonists cause hypothermia by an on‐target action: on TRPV1 channels on abdominal sensory nerves. These channels are tonically activated by protons and drive the reflectory inhibition of thermogenesis and tail‐skin vasoconstriction. Those TRPV1 antagonists that cause hypothermia further inhibit these cold defences, thus decreasing body temperature.SignificanceTRPV1 antagonists (of capsaicin activation) are highly unusual in that they can cause both hyper‐ and hypothermia by modulating the same mechanism. For drug development, this means that both side effects can be dealt with simultaneously, by minimizing these compounds’ interference with TRPV1 activation by protons.

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“…3) Furthermore, blood flow is regulated by various factors such as nitric oxide (NO) 4) and prostanoids, 5) and the autonomic nerve system. 6) NO plays important roles including causing vasodilatation in the endothelium and controlling physiological conditions. It also activates guanylate cyclase, which catalyzes cyclic GMP (cGMP) production from guanosine triphosphate, in smooth muscle cells.…”

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confidence: 99%

2-Ethylpyrazine Induces Vasodilatation by Releasing Nitric Oxide in the Endothelium

Ashigai

Ikeshima

Koizumi

et al. 2017

Biological & Pharmaceutical Bulletin

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Oxygen transportation and regulation of some physiological processes are facilitated by blood flow. Furthermore, blood flow is regulated by various factors such as nitric oxide (NO) and the autonomic nerve system. In modern life, many people suffer from chilliness (hiesho) because of mental stress and an excessive use air-conditioning systems, which induces vasoconstriction in the peripheral skin. In this study, we focused on pyrazine derivatives, particularly compounds that are used as food flavoring materials, and investigated their effects on vascular function and blood flow. We examined the vasodilatory effect of pyrazine derivatives in the rat thoracic aorta and found 2-ethylpyrazine (2-EP) to be the most active pyrazine compound. Additionally, we found that 2-EP induces vasodilatation through the activities of endothelium-derived relaxing factors. 2-EP activates NO synthesis through the effect of endothelial NO synthase in the endothelium. As a result, cyclic GMP levels rise in smooth muscle cells and vasodilatation is induced. We also confirmed that 2-EP increases peripheral blood flow in rats. From these results, we concluded that 2-EP induces vasodilatation by inducing the release of NO and increasing peripheral blood flow.

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The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature

Cited by 55 publications

References 59 publications

Tail‐Cuff Technique and Its Influence on Central Blood Pressure in the Mouse

Tail‐Cuff Technique and Its Influence on Central Blood Pressure in the Mouse

TRPV1 antagonists that cause hypothermia, instead of hyperthermia, in rodents: Compounds’ pharmacological profiles, in vivo targets, thermoeffectors recruited and implications for drug development

2-Ethylpyrazine Induces Vasodilatation by Releasing Nitric Oxide in the Endothelium

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