Voluntary locomotion linked with cerebral activation is mediated by vasopressin V1a receptors in free‐moving mice

Abstract

Key points• Arterial blood pressure rises at the onset of voluntary locomotion, which is probably advantageous for increasing blood flow to contracting muscles without delay.• We previously reported in free-moving mice that the feedback control of arterial blood pressure through peripheral baroreceptors, which was dominant at rest, was suppressed during activation of the cerebral cortex; however, no neurotransmitter for the mechanisms has been identified.• Central suppression of the feedback control of arterial blood pressure at the onset of voluntary locomotion was abolished in vasopressin V1a receptor-deficient mice and by local infusion of a V1a receptor antagonist into the brainstem area, termed the nucleus tractus solitarii, of control mice.• Thus, central vasopressin might play an important role as a neurotransmitter in the pressor response at the onset of voluntary locomotion.Abstract We previously reported that cerebral activation suppressed baroreflex control of heart rate (HR) at the onset of voluntary locomotion. In the present study, we examined whether vasopressin V1a receptors in the brain were involved in these responses by using free-moving V1a receptor knockout (KO, n = 8), wild-type mice locally infused with a V1a receptor antagonist into the nucleus tractus solitarii (BLK, n = 8) and control mice (CNT, n = 8). Baroreflex sensitivity ( HR/ MAP) was determined from HR response ( HR) to a spontaneous change in mean arterial pressure ( MAP) every 4 s during the total resting period, which was ∼8.7 h, of the 12 h measuring period in the three groups. HR/ MAP was determined during the periods when the cross-correlation function (R(t)) between HR and MAP was significant (P < 0.05). Cerebral activity was determined from the power density ratio of θ to δ wave band (θ/δ) on the electroencephalogram every 4 s. Spontaneous changes in θ/δ were significantly correlated with R(t) during 62 ± 3% of the total resting period in CNT (P < 0.05), but only 38 ± 4% in KO and 47 ± 2% in BLK (vs. CNT, both P < 0.001). When R(t) and HR/ MAP were divided into six bins according to the level of θ/δ, both were positively correlated with θ/δ in CNT (both P < 0.001), while neither was correlated in KO or BLK (all P > 0.05). Moreover, the probability that mice started to move after an increase in θ/δ was 24 ± 4% in KO and 24 ± 6% in BLK, markedly lower than 61 ± 5% in CNT (both P < 0.001), with no suppression of the baroreflex control of HR. Abbreviations AVP, arginine vasopressin; CBF, cerebral blood flow; CNT, control; EEG, electroencephalogram; HR, heart rate; MAP, mean arterial pressure; NTS, nucleus tractus solitarii; REM, rapid eye movement; R(t), cross-correlation function between spontaneous changes in HR and MAP; V1a BLK, V1a receptor blockade; V1a KO, V1a receptor knockout; WT, wild-type; Z R (t) , transformed R(t); HR/ MAP, HR response to the spontaneous change in MAP; θ/δ, the power density ratio of θ to δ wave band in EEG.

Salt-induced sympathoexcitation involves vasopressin V1a receptor activation in the paraventricular nucleus of the hypothalamus

“…Taken together, these findings demonstrate that AVP contributes to the sympathoexcitation and high blood pressure induced by either acute or chronic osmotic challenges, which involves activation of via V 1a receptors within the PVN. Although we cannot discount it entirely, given the dose, the small injection volume, and the fact that the PVN has an intact blood-brain barrier, it is highly unlikely that the V 1a receptor antagonist leaked into the circulation to block V 1a receptors located in the periphery (27).…”

Vasopressin V1a receptor gene and voluntary exercise: Insights from humans and animal models

“…To assess this, we measured mean arterial pressure (MAP, arterial catheter), HR, and electroencephalogram (EEG) in freely moving male V1a KO (n = 8) and wildtype mice (WT, n = 8) 31) . Baroreflex sensitivity (ΔHR/ ΔMAP) was determined from HR response (ΔHR) to a .…”

“…7, the probability of voluntary locomotion was highly correlated with the suppression of baroreflex control of HR after cerebral activation. Thus, central V1a receptors might play an important role in facilitating voluntary locomotion after cerebral activation by suppressing baroreflex control of HR 31) .…”

Physical Activity, Exercise, Sedentary Behavior and Health

“…To assess this, we measured mean arterial pressure (MAP, arterial catheter), HR, and electroencephalogram (EEG) in free-moving male V1a KO (n = 8) and wildtype mice (WT, n = 8) (Masuki et al 2013 ). Barorefl ex sensitivity (ΔHR/ΔMAP) was determined from HR response (ΔHR) to a spontaneous change in MAP (ΔMAP) every 4 s during the total resting period which was ~8.7 h of the 12-h measuring period in both groups.…”

“…We found a signifi cant and high correlation between them (R 2 = 0.66, P < 0.001), indicating that the probability of locomotion after cerebral activation is reduced when linkage between cerebral activity and barorefl ex control of HR is impaired(Figure fromMasuki et al 2013 ) *Values were averaged after z transformation.…”