Effects of pituitary adenylate cyclase-activating polypeptide on cardiovascular and respiratory responses in anaesthetised dogs

Runcie, Myfanwy Jane; Ulman, Lesley G.; Potter, Erica K.

doi:10.1016/0167-0115(95)00131-x

Cited by 42 publications

(29 citation statements)

References 16 publications

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“…Moreover, the response of the guinea pig heart was blocked by atropine, indicating that the negative chronotropic effect is mediated by cholinergic neurons (Chang et al, 2005). On the contrary, the positive effects of PACAP are attributable to direct stimulation of cardiac myocytes Runcie et al, 1995;Hirose et al, 1997a;Chang et al, 2005). In isolated rat and guinea pig heart preparations, which lack sympathetic tone, PACAP causes tachycardia independently of adrenergic mechanisms (Chang et al, 2005).…”

Section: Pituitary Adenylate Cyclase-activating Polypeptidementioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

et al. 2009

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Section: Pituitary Adenylate Cyclase-activating Polypeptidementioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

et al. 2009

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“…One possibility is that the impaired chemoreflex in PACAP-deficient mice that we previously reported (8) is exacerbated by cooling. Several reports suggest that intravenous injections of PACAP can have acute effects on V E in adult animals, possibly by acting directly on the carotid body (15,35). Interestingly, the carotid bodies have also been implicated in thermoregulation (20).…”

Section: Mechanism Of Action Of Pacap In Breathing During Coolingmentioning

confidence: 99%

Pituitary adenylate cyclase-activating polypeptide maintains neonatal breathing but not metabolism during mild reductions in ambient temperature

Cummings¹,

Willie²,

Wilson³

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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mice at this age are also vulnerable to prolonged apneas and sudden death. From these observations, we hypothesized that before the onset of genotype-specific mortality and in the absence of anesthetic, the breathing of PACAP-deficient mice is more susceptible to mild reductions in ambient temperature than wild-type littermates. To test this hypothesis, we recorded breathing in one group of postnatal day 4 PACAP ϩ/ϩ , ϩ/Ϫ , and Ϫ/Ϫ neonates (using unrestrained, flowthrough plethysmography) and metabolic rate in a separate group (using indirect calorimetry), both of which were exposed acutely to ambient temperatures slightly below (29°C), slightly above (36°C), or at thermoneutrality (32°C). At 32°C, the breathing frequency of PACAP Ϫ/Ϫ neonates was significantly less than PACAP ϩ/ϩ littermates. Reducing the ambient temperature to 29°C caused a significant suppression of tidal volume and ventilation in both PACAP ϩ/Ϫ and Ϫ/Ϫ animals, while the tidal volume and ventilation of PACAP ϩ/ϩ animals remained unchanged. Genotype had no effect on the ventilatory responses to ambient warming. At all three ambient temperatures, genotype had no influence on oxygen consumption or body temperature. These results suggest that during mild reductions in ambient temperature, PACAP is vital for the preservation of neonatal tidal volume and ventilation, but not for metabolic rate or body temperature. neonatal apnea; temperature; metabolism; hypoxia; neonatal apnea; sudden infant death syndrome THE PRIMARY ROLE OF THE RESPIRATORY control system is to couple ventilation (V E) to changes in metabolic rate for the maintenance of blood gases. In small neonatal rodents, a drop in ambient temperature just outside the thermoneutral zone initiates nonshivering thermogenesis and an increase in oxygen consumption (V O 2 ). Despite this metabolic response, the body temperature of small neonatal rodents continues to fall with ambient temperature, owing to their large surface area-tovolume ratio (28). This causes a potential problem for the neonatal respiratory control system; a fall in body temperature has a suppressive effect on neuronal function, including those involved in the control of breathing [Q 10 effect: (27,36,41)]. Neonates must therefore have compensatory mechanisms to mitigate the Q 10 effect and maintain the tight coupling between V E and metabolic rate.Pituitary adenylate cyclase-activating polypeptide (PACAP) has potent modulatory effects on both the central and peripheral nervous systems. The primary structure of PACAP is remarkably constrained throughout evolution, suggesting one or more critical developmental and/or physiological roles (38). PACAP stimulates three classes of G protein-coupled receptors that utilize cAMP and phosphoinosotide species to produce its cellular effects (42). At the system level, PACAP has been implicated in the proliferation, differentiation, and survival of neural progenitor cells within the central nervous system (30,31,43). However, PACAP is also involved in a range of acute physiological proces...

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“…Peripheral administration of PACAP-38 (PACAP) dilates blood vessels, causing hypotension (42,53). Centrally acting PACAP is sympathoexcitatory and, in most studies, pressor (13, 16 -18, 26, 30, 56).…”

mentioning

confidence: 99%

PACAP causes PAC₁/VPAC₂ receptor mediated hypertension and sympathoexcitation in normal and hypertensive rats

Farnham

Lung

Tallapragada

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Farnham MM, Lung MS, Tallapragada VJ, Pilowsky PM. PACAP causes PAC 1/VPAC2 receptor mediated hypertension and sympathoexcitation in normal and hypertensive rats. Am J Physiol Heart Circ Physiol 303: H910 -H917, 2012. First published August 10, 2012; doi:10.1152/ajpheart.00464.2012.-Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide that plays an important role in hypertension and stress responses. PACAP acts at three G protein-coupled receptors [PACAP type 1 receptor (PAC 1 ) and vasoactive intestinal peptide receptor types 1 and 2 (VPAC 1 and VPAC2)] and is localized to sites involved in cardiovascular control, most significantly the rostral ventrolateral medulla (RVLM). The RVLM is crucial for the tonic and reflex control of efferent sympathetic activity. Increases in sympathetic activity are observed in most types of hypertension and heart failure. PACAP delivered intrathecally also causes massive sympathoexcitation. We aimed to determine the presence and abundance of the three PACAP receptors in the RVLM, the role, in vivo, of PACAP in the RVLM on tonic and reflex cardiovascular control, and the contribution of PACAP to hypertension in the spontaneously hypertensive rat (SHR). Data were obtained using quantitative PCR and microinjection of PACAP and its antagonist, PACAP(6 -38), into the RVLM of anesthetized artificially ventilated normotensive rats or SHRs. All three receptors were present in the RVLM. PACAP microinjection into the RVLM caused sustained sympathoexcitation and tachycardia with a transient hypertension but did not affect homeostatic reflexes. The responses were partially mediated through PAC1/VPAC2 receptors since the effect of PACAP was attenuated (ϳ50%) by PACAP(6 -38). PACAP was not tonically active in the RVLM in this preparation because PACAP(6 -38) on its own had no inhibitory effect. PACAP has long-lasting cardiovascular effects, but altered PACAP signaling within the RVLM is not a cause of hypertension in the SHR. blood pressure; rostral ventrolateral medulla; sympathetic; neuropeptides; pituitary adenylate cyclase-activating polypeptide; vasoactive intestinal peptide receptor PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP) exists in discrete regions of the brain stem and spinal cord involved in cardiovascular control, one of which is the rostral ventrolateral medulla (RVLM) (7,12,17,22,35,59). The RVLM is crucial for cardiovascular control (20,40,48,49) as it contains the neurons that determine resting mean arterial pressure (MAP) and responds to the activation of adaptive reflexes (11,21,37,38,51). Changes in autonomic function resulting from activation of the baroreceptor, somatosympathetic, and chemoreceptor reflexes are all principally mediated by increasing or decreasing the activity of RVLM neurons, which, in turn, project to and excite sympathetic preganglionic neurons in the thoracolumbar spinal cord (28,36,39,43,44,49,62).Peripheral administration of PACAP-38 (PACAP) dilates blood vessels, causing hypotension (42, 53). Centra...

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Effects of pituitary adenylate cyclase-activating polypeptide on cardiovascular and respiratory responses in anaesthetised dogs

Cited by 42 publications

References 16 publications

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Pituitary adenylate cyclase-activating polypeptide maintains neonatal breathing but not metabolism during mild reductions in ambient temperature

PACAP causes PAC₁/VPAC₂ receptor mediated hypertension and sympathoexcitation in normal and hypertensive rats

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Effects of pituitary adenylate cyclase-activating polypeptide on cardiovascular and respiratory responses in anaesthetised dogs

Cited by 42 publications

References 16 publications

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Pituitary adenylate cyclase-activating polypeptide maintains neonatal breathing but not metabolism during mild reductions in ambient temperature

PACAP causes PAC1/VPAC2 receptor mediated hypertension and sympathoexcitation in normal and hypertensive rats

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PACAP causes PAC₁/VPAC₂ receptor mediated hypertension and sympathoexcitation in normal and hypertensive rats