Baroreceptor‐mediated inhibition of respiration after peripheral and central administration of a 5‐HT_1A receptor agonist in neonatal piglets

Abstract

Inhibition of neurones in the ventral medulla accentuates the respiratory inhibition associated with acute blood pressure elevation in piglets. Activation of presynaptic 5-HT 1A receptors inhibits serotonergic neurones in the ventral medulla and caudal raphé, and we tested the hypothesis that administration of 8-hydroxydipropylaminotetralin (8-OH-DPAT), a 5-HT 1A agonist, within the rostroventral medulla and caudal raphé would enhance baroreceptor-mediated inhibition of respiratory activity in decerebrate, neonatal piglets. Baroreceptor stimulation was achieved by inflating a balloon in the distal aorta to elevate carotid blood pressure. After two to four control trials of baroreceptor stimulation, each piglet was given either a single intravenous (I.V.) dose of 10 μg kg -1 8-OH-DPAT or treated by adding 10 or 30 mM 8-OH-DPAT to the dialysate for ∼10 min to inhibit serotonergic neurones, after which the baroreceptor stimulation trials were repeated. Baroreceptor stimulation reduced respiratory activity, particularly the respiratory frequency, which diminished from 35.7 ± 3.3 to 33.8 ± 3.1 breaths min -1 (P < 0.02) and, following I.V. 8-OH-DPAT, baroreceptor-mediated inhibition of respiratory output was significantly accentuated (P < 0.05); the respiratory frequency declined from 34.5 ± 3.6 to 26.5 ± 2.9 breaths min -1 . Increasing aortic blood pressure reduced the respiratory frequency (P < 0.01), but focal dialysis of 10 or 30 mM 8-OH-DPAT had, on average, no effect on the ventilatory inhibition associated with an acute elevation of blood pressure. We conclude that activation of 5-HT 1A receptors after systemic administration of 8-OH-DPAT enhanced baroreflex-mediated inhibition of ventilation, but this effect cannot be attributed to 5-HT 1A receptor activation within the rostroventral medulla and caudal raphé.

Neonatal transient respiratory depression after maternal urapidil infusion for hypertension

“…Urapidil is known to cross the placenta and, consequently, (side-)effects can be anticipated. This is supported by a recent study of Curran and Leiter showing the impact of the central 5-HT1 agonist on respiratory drive in neonatal piglets [1,6].…”

“…Goda et al showed that a bolus intravenous administration of 5-HT immediately produced apnea in rats [2,3]. Curran and Leiter recently reported on the impact of the central 5-HT1 agonist on respiratory drive in neonatal piglets by baroreceptor stimulation [1].…”

“…However, clinical experiences with this drug have only been published in a very few reports, and there have been only limited observations on the (side-)effects of urapidil on the neonate. Maternal drug use may exert unwanted effects on the foetus and neonate by a direct pharmacological action of the drug following its passage through the placenta [1]. This transfer has been proven by Schulz et al [6] and can be anticipated based on the limited albumin binding (< 50%) of this drug [4].…”

Brainstem mechanisms underlying the sudden infant death syndrome: Evidence from human pathologic studies

“…Extensive animal data indicate that 5-HT influences multiple homeostatic functions mediated by the medulla, including: (1) central chemoreception to carbon dioxide and/or oxygen (Bradley et al, 2002;Nattie, Li, Richerson, & Lappi, 2004;Taylor, Li, Green, Kinney, & Nattie, 2004;Wang, Tiwari, Bradley, Zaykin, & Richerson, 2001); (2) medullary respiratory rhythm generation during development (Bou-Flores et al, 2000); (3) maturation of the medullary and phrenic respiratory network in prenatal development (Bou-Flores et al, 2000); (4) cardiovascular function (Curran & Leiter, 2007;Pelaez, Schreihofer, & Guyenet, 2002); (5) thermoregulation Nagai, 1992;Ootsuka & Blessing, 2006); (6) upper airway control (Gao & Mason, 2001;Hilaire, Morin, Lajard, & Monteau, 1993;Monteau, Morin, Hennequin, & Hilaire, 1990); (7) respiratory rhythm generation (Gunther, Maroteaux, & Schwarzacher, 2006;Pena & Ramirez, 2002), and (8) sleep/waking cycles (Brown, Sirlin, Benoit, Hoffman, & Darnall, 2007). A distinct feature of 5-HT neurons is that they exhibit differential firing rates according to the level of arousal, with increased firing during waking, decreased firing during NREM, and almost complete absence of firing during REM (McGinty & Harper, 1976;Trulson & Jacobs, 1979).…”

Neonatal stress and attenuation of the hypercapnic ventilatory response in adult male rats: the role of carotid chemoreceptors and baroreceptors

“…During hypercapnia, CO 2 increases mean arterial blood pressure by a direct effect on vessels and by sympathetic activation (13,23,32). This increase in blood pressure activates baroreceptors that modulate respiratory activity and decreases breathing frequency (9,25). Therefore, the baroreflex potentiation is another mechanism by which NMS could attenuate the HCVR.…”