Sequence of excitation as a factor in sympathetic-parasympathetic interactions in the heart.

Yang, Tianen; Levy, Matthew N.

doi:10.1161/01.res.71.4.898

Cited by 43 publications

(25 citation statements)

References 33 publications

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“…Neuropeptide Y released from sympathetic nerve terminals also interacts with ACh [8,11,47,48]. Conversely, the release of neuropeptide Y is prevented by simultaneous vagal stimulation [9,24]. As these studies have demonstrated mutually inhibitory prejunctional interactions, the phenomenon of bidirectional augmentation of dynamic heart rate regulation could not be directly explained.…”

Section: Prejunctional Mechanism Of Vago-sympathetic Interactionmentioning

confidence: 93%

“…Yang and Levy [24], however, demonstrated that the longer the antecedent sympathetic stimulation continued, the less prominent was the vagal effect on the heart rate, even though the heart rate achieved by antecedent sympathetic stimulation was at a similar level. The prolonged sympathetic stimulation accumulated neuropeptide Y at the neuroeffector junction, which inhibited the vagal effect on the heart rate.…”

Section: Functional Characteristics Of Dynamic Bidirectional Augmentamentioning

confidence: 95%

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Dynamic nonlinear vago-sympathetic interaction in regulating heart rate

1998

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Although the characteristics of the static interactions between the sympathetic and parasympathetic nervous systems in regulating heart rate have been well established, how the dynamic interaction modulates the heart rate response remains unknown. Thus, we investigated the dynamic interaction by estimating the transfer function from nerve stimulation to heart rate, using band-limited Gaussian white noise, in anesthetized rabbits. Concomitant tonic vagal stimulation at 5 and 10 Hz increased the gain of the transfer function relating dynamic sympathetic stimulation to heart rate by 55.0%+/-40.1% and 80.7%+/-50.5%, respectively (P < 0.05). Concomitant tonic sympathetic stimulation at 5 and 10 Hz increased the gain of the transfer function relating dynamic vagal stimulation to heart rate by 18.2%+/-17.9% and 24.1%+/-18.0%, respectively (P < 0.05). Such bidirectional augmentation was also observed during simultaneous dynamic stimulation of the sympathetic and vagal nerves independent of their stimulation patterns. Because of these characteristics, changes in sympathetic or vagal tone alone can alter the dynamic heart rate response to stimulation of the other nerve. We explained this phenomenon by assuming a sigmoidal static relationship between autonomic nerve activity and heart rate. To confirm this assumption, we identified the static and dynamic characteristics of heart rate regulation by a neural network analysis, using large-amplitude Gaussian white noise input. To examine the mechanism involved in the bidirectional augmentation, we increased cytosolic adenosine 3',5'-cyclic monophosphate (cAMP) at the postjunctional effector site by applying pharmacological interventions. The cAMP accumulation increased the gain of the transfer function relating dynamic vagal stimulation to heart rate. Thus, accumulation of cAMP contributes, at least in part, to the sympathetic augmentation of the dynamic vagal control of heart rate.

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Section: Prejunctional Mechanism Of Vago-sympathetic Interactionmentioning

confidence: 93%

Section: Functional Characteristics Of Dynamic Bidirectional Augmentamentioning

confidence: 95%

Dynamic nonlinear vago-sympathetic interaction in regulating heart rate

1998

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“…For example, cardiac sympathetic nerves release NPY 1-36 directly into the myocardium (35,52,55). Moreover, as discussed by Sosunov et al (46), the heart releases NPY 1-36 from intrinsic intracardiac neurons and granular-containing cells.…”

Section: New and Noteworthymentioning

confidence: 95%

NPY_1–36and PYY_1–36activate cardiac fibroblasts: an effect enhanced by genetic hypertension and inhibition of dipeptidyl peptidase 4

Zhu

Gillespie

Jackson

2015

American Journal of Physiology-Heart and Circulatory Physiology

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Cardiac sympathetic nerves release neuropeptide Y (NPY)1-36, and peptide YY (PYY)1-36 is a circulating peptide; therefore, these PP-fold peptides could affect cardiac fibroblasts (CFs). We examined the effects of NPY1-36 and PYY1-36 on the proliferation of and collagen production ([(3)H]proline incorporation) by CFs isolated from Wistar-Kyoto (WKY) normotensive rats and spontaneously hypertensive rats (SHRs). Experiments were performed with and without sitagliptin, an inhibitor of dipeptidyl peptidase 4 [DPP4; an ectoenzyme that metabolizes NPY1-36 and PYY1-36 (Y1 receptor agonists) to NPY3-36 and PYY3-36 (inactive at Y1 receptors), respectively]. NPY1-36 and PYY1-36, but not NPY3-36 or PYY3-36, stimulated proliferation of CFs, and these effects were more potent than ANG II, enhanced by sitagliptin, blocked by BIBP3226 (Y1 receptor antagonist), and greater in SHR CFs. SHR CF membranes expressed more receptor for activated C kinase (RACK)1 [which scaffolds the Gi/phospholipase C (PLC)/PKC pathway] compared with WKY CF membranes. RACK1 knockdown (short hairpin RNA) and inhibition of Gi (pertussis toxin), PLC (U73122), and PKC (GF109203X) blocked the proliferative effects of NPY1-36. NPY1-36 and PYY1-36 stimulated collagen production more potently than did ANG II, and this was enhanced by sitagliptin and greater in SHR CFs. In conclusion, 1) NPY1-36 and PYY1-36, via the Y1 receptor/Gi/PLC/PKC pathway, activate CFs, and this pathway is enhanced in SHR CFs due to increased localization of RACK1 in membranes; and 2) DPP4 inhibition enhances the effects of NPY1-36 and PYY1-36 on CFs, likely by inhibiting the metabolism of NPY1-36 and PYY1-36. The implications are that endogenous NPY1-36 and PYY1-36 could adversely affect cardiac structure/function by activating CFs, and this may be exacerbated in genetic hypertension and by DPP4 inhibitors.

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“…These sympathetic neurons primarily utilize norepinephrine as their principal neurotransmitter, although other neuropeptides, such as neuropeptide Y (NPY) and galanin, are also co-released from sympathetic terminals 11 , 12 . Among other functions, NPY and galanin decrease acetylcholine release from adjacent parasympathetic terminals 13 - 16 . Parasympathetic neurons receive pre-ganglionic inputs from the vagus and have their cell bodies within the cardiac ganglia (Fig.…”

Section: Introductionmentioning

confidence: 99%

Autonomic cardiac innervation

Hasan

2013

Organogenesis

126

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Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these “non-classical” cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development. Cardiac autonomic nerves are closely spatially associated in cardiac plexuses, ganglia and pacemaker regions and so are sensitive to release of neurotransmitter, neuropeptides and trophic factors from adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within the two arms of the autonomic system that is critical for disease progression. Although this crosstalk between sympathetic and parasympathetic nerves has been well established for adult nerves, it is unclear whether a degree of paracrine regulation occurs across the autonomic limbs during development. Aberrant nerve remodeling is a common occurrence in many adult cardiovascular pathologies, and the mechanisms regulating outgrowth or denervation are disparate. However, autonomic neurons display considerable plasticity in this regard with neurotrophins and inflammatory cytokines having a central regulatory function, including in possible neurotransmitter changes. Certainly, neurotrophins and cytokines regulate transcriptional factors in adult autonomic neurons that have vital differentiation roles in development. Particularly for parasympathetic cardiac ganglion neurons, additional examinations of developmental regulatory mechanisms will potentially aid in understanding attenuated parasympathetic function in a number of conditions, including heart failure.

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Sequence of excitation as a factor in sympathetic-parasympathetic interactions in the heart.

Cited by 43 publications

References 33 publications

Dynamic nonlinear vago-sympathetic interaction in regulating heart rate

Dynamic nonlinear vago-sympathetic interaction in regulating heart rate

NPY_1–36and PYY_1–36activate cardiac fibroblasts: an effect enhanced by genetic hypertension and inhibition of dipeptidyl peptidase 4

Autonomic cardiac innervation

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Sequence of excitation as a factor in sympathetic-parasympathetic interactions in the heart.

Cited by 43 publications

References 33 publications

Dynamic nonlinear vago-sympathetic interaction in regulating heart rate

Dynamic nonlinear vago-sympathetic interaction in regulating heart rate

NPY1–36and PYY1–36activate cardiac fibroblasts: an effect enhanced by genetic hypertension and inhibition of dipeptidyl peptidase 4

Autonomic cardiac innervation

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NPY_1–36and PYY_1–36activate cardiac fibroblasts: an effect enhanced by genetic hypertension and inhibition of dipeptidyl peptidase 4