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Raised arterial blood pressure in neurokinin-1 receptor-deficient mice (NK1R−/−): evidence for a neural rather than a vascular mechanism

Moyes, AJ; Stanford, SC; Hosford, PS; Hobbs, AJ; Ramage, AG; (2016) Raised arterial blood pressure in neurokinin-1 receptor-deficient mice (NK1R−/−): evidence for a neural rather than a vascular mechanism. Experimental Physiology , 101 (5) pp. 588-598. 10.1113/EP085347. Green open access

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Abstract

NEW FINDINGS: What is the central question of this study? Does genetic ablation of neurokinin-1 receptors alter arterial blood pressure? What is the main finding and its importance? NK1R(-/-) mice have increased mean arterial blood pressure, but without a concomitant change in vascular reactivity. This finding suggests that neurokinin-1 receptors play a role in the neural regulation of blood pressure. Mice with functional ablation of the neurokinin-1 receptor gene, Tacr1, (NK1R(-/-) ) express behavioural abnormalities equivalent to those seen in attention deficit hyperactivity disorder (ADHD). An established model of ADHD is the spontaneously hypertensive rat, which exhibits high blood pressure owing to increased central sympathetic drive. In light of the evidence that the neurokinin-1 receptor (NK1R) also influences cardiovascular haemodynamics, we have investigated whether NK1R(-/-) mice exhibit raised blood pressure. Cardiovascular parameters were recorded for 24 h in conscious mice using radiotelemetry. Vascular function was assessed in mesenteric resistance arteries by wire myography. The NK1R(-/-) mice exhibited a higher blood pressure than wild-type animals throughout the 24 h period. Heart rate and locomotor activity in NK1R(-/-) mice were higher than in wild-type mice during the night period (active phase), consistent with an ADHD-like phenotype, but not during the day. Mesenteric and renal arteries from NK1R(-/-) mice exhibited normal vascular function; the responses to vasoconstrictors (U46619 and phenylephrine) and the endothelium-dependent vasodilator, acetylcholine, were not altered in these animals, suggesting that the NK1R does not regulate vascular tone. Analysis of heart rate variability revealed a higher low-frequency to high-frequency ratio in NK1R(-/-) mice, indicative of increased cardiac sympathetic activity. We propose that the raised blood pressure in NK1R(-/-) mice could be due to a neural mechanism rather than a change in vascular reactivity. Further studies are required to understand this mechanism and to establish whether a subgroup of ADHD patients with polymorphism of the equivalent (TACR1) gene are affected in a similar way.

Type: Article
Title: Raised arterial blood pressure in neurokinin-1 receptor-deficient mice (NK1R−/−): evidence for a neural rather than a vascular mechanism
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1113/EP085347
Publisher version: http://dx.doi.org/10.1113/EP085347
Language: English
Additional information: This is the peer reviewed version of the following article: Moyes, AJ; Stanford, SC; Hosford, PS; Hobbs, AJ; Ramage, AG; (2016) Raised arterial blood pressure in neurokinin-1 receptor-deficient mice (NK1R−/−): evidence for a neural rather than a vascular mechanism. Experimental Physiology, 101 (5) pp. 588-598, which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html#terms).
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1483150
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