Action and localization of vasoactive intestinal peptide in the coronary circulation: Evidence for nonadrenergic, noncholinergic coronary regulation

Key pointsr Intrinsic cardiac (IC) neurons undergo differential morphological and phenotypic remodelling that reflects the site of myocardial infarction (MI).r Afferent neural signals from the infarcted region to IC neurons are attenuated, while those from border and remote regions are preserved post-MI, giving rise to a 'neural sensory border zone' .r Convergent IC local circuit (processing) neurons have enhanced transduction capacity following MI.r Functional network connectivity within the intrinsic cardiac nervous system is reduced post-MI.r MI reduces the response and alters the characteristics of IC neurons to ventricular pacing.Abstract Autonomic dysregulation following myocardial infarction (MI) is an important pathogenic event. The intrinsic cardiac nervous system (ICNS) is a neural network located on the heart that is critically involved in autonomic regulation. The aims of this study were to characterize structural and functional remodelling of the ICNS post-MI in a porcine model (control (n = 16) vs. healed anteroapical MI (n = 16)). In vivo microelectrode recordings of basal activity, as well as responses to afferent and efferent stimuli, were recorded from intrinsic cardiac neurons. From control 118 neurons and from MI animals 102 neurons were functionally classified as afferent, efferent, or convergent (receiving both afferent and efferent inputs). In control and MI, convergent neurons represented the largest subpopulation (47% and 48%, respectively) and had enhanced transduction capacity following MI. Efferent inputs to neurons were maintained post-MI. Afferent inputs were attenuated from the infarcted region (19% in control vs. 7% in MI; P = 0.03), creating a 'neural sensory border zone' , or heterogeneity in afferent information. MI reduced transduction of changes in preload (54% in control vs. 41% in MI; P = 0.05). The overall functional network connectivity, or the ability of neurons to respond to independent pairs of stimuli, within the ICNS was reduced following MI. The neuronal response was differentially decreased to ventricular vs. atrial pacing post-MI (63% in control vs. 44% in MI to ventricular pacing; P < 0.01). MI induced morphological and phenotypic changes within the ICNS. The alteration of afferent neural signals, and remodelling of convergent neurons, represents a 'neural signature' of ischaemic heart disease.

show abstract

“…VIP is known to act as a coronary vasodilator and have inotropic and chronotropic effects (Weihe & Reinecke, ; Brum et al . ; Frase et al . ).…”

Section: Discussionmentioning

confidence: 99%

Myocardial infarction induces structural and functional remodelling of the intrinsic cardiac nervous system

Rajendran

Nakamura

Ajijola

et al. 2015

The Journal of Physiology

127

145

View full text Add to dashboard Cite

show abstract

“…Possible candidates for peptidergic vasodilation include substance P (endothelium-dependent vasodilation) and vasoactive intestinal peptide (endotheliumindependent vasodilation), both of which have been demonstrated in other circulations. 7,24 The paradoxical vasodilation is probably manifested in women and patients with Raynaud's disease because of their elevated sympathetic tone. When sympathetic tone was increased in men by total body cooling, mental arithmetic and deep inspiration induced a paradoxical vasodilation.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in control of cutaneous blood flow.

et al. 1990

View full text Add to dashboard Cite

Women are far more likely than men to suffer from Raynaud's disease. The purpose of this study was to determine whether there are gender differences in local or central control of cutaneous blood flow that could account for the increased incidence of Raynaud's disease in women. To assess cutaneous blood flow, hand blood flow (HBF), finger blood flow (FBF), or skin perfusion (SP) was measured by fluid plethysmography, mercury strain-gauge plethysmography, or laser Doppler spectroscopy, respectively, in 47 volunteers. Basal HBF in men exceeded that of women (12.1±2.0 versus 6.2±1.5 mlU100 ml/min). Likewise, FBF in men surpassed that of women (19.5±4.1 versus 7.7±1.8 ml/100 mlVmin). Similarly, SP in men was greater than that of women (270±42 versus 81±16 perfusion units). However, after total body warming (to induce a thermal sympatholysis), HBF in women exceeded that of men, suggesting that the lower basal HBF in women was due to increased sympathetic outflow to the extremities. Mental stress and deep inspiration reduced HBF and SP in men. Paradoxically, both of these maneuvers increased HBF and SP in women. To determine whether these paradoxical responses in women were due to the women's elevated basal sympathetic tone, these experiments were repeated after total body cooling in men to increase sympathetic tone and after total body warming in women to reduce sympathetic tone. Total body cooling reduced HBF and SP in men. Under these conditions, mental stress and deep inspiration induced vasodilation. In women, total body warming for 10 minutes increased HBF. Under these conditions, mental stress and deep inspiration induced vasoconstriction. In conclusion, basal cutaneous blood flow is reduced in women. This appears to be due to a basal increase in sympathetic tone rather than to a local structural or functional difference in the cutaneous circulation. In addition, a paradoxical vasodilation in response to mental arithmetic and deep inspiration is unmasked at high levels of sympathetic tone. The gender differences in cutaneous blood flow may account for the increased incidence of Raynaud's disease in young women. (Circulation 1990;82:1607-1615

show abstract

“…Right heart failure is a hallmark of severe PAH, and ultimately leading to death. In animals and in humans, infusion of VIP increases the epicardial coronary artery cross-sectional area by 27%, decreases coronary vascular resistance by 46%, and increases coronary artery blood flow by 200% [20,86]. Application of VIP to patients also increases the left ventricular fraction shortening by 38% and significantly increases left ventricular contractility [86,87].…”

Section: Therapeutic Potential Of Vip In Pahmentioning

confidence: 99%

Prospect of vasoactive intestinal peptide therapy for COPD/PAH and asthma: a review

Lee

Sung

2011

Respir Res

View full text Add to dashboard Cite

There is mounting evidence that pulmonary arterial hypertension (PAH), asthma and chronic obstructive pulmonary disease (COPD) share important pathological features, including inflammation, smooth muscle contraction and remodeling. No existing drug provides the combined potential advantages of reducing vascular- and bronchial-constriction, and anti-inflammation. Vasoactive intestinal peptide (VIP) is widely expressed throughout the cardiopulmonary system and exerts a variety of biological actions, including potent vascular and airway dilatory actions, potent anti-inflammatory actions, improving blood circulation to the heart and lung, and modulation of airway secretions. VIP has emerged as a promising drug candidate for the treatment of cardiopulmonary disorders such as PAH, asthma, and COPD. Clinical application of VIP has been limited in the past for a number of reasons, including its short plasma half-life and difficulty in administration routes. The development of long-acting VIP analogues, in combination with appropriate drug delivery systems, may provide clinically useful agents for the treatment of PAH, asthma, and COPD. This article reviews the physiological significance of VIP in cardiopulmonary system and the therapeutic potential of VIP-based agents in the treatment of pulmonary diseases.

show abstract

Action and localization of vasoactive intestinal peptide in the coronary circulation: Evidence for nonadrenergic, noncholinergic coronary regulation

Cited by 46 publications

References 24 publications

Myocardial infarction induces structural and functional remodelling of the intrinsic cardiac nervous system

Myocardial infarction induces structural and functional remodelling of the intrinsic cardiac nervous system

Sex differences in control of cutaneous blood flow.

Prospect of vasoactive intestinal peptide therapy for COPD/PAH and asthma: a review

Contact Info

Product

Resources

About