vasoactive-intestinal-peptide and Lung-Diseases

Vasoactive intestinal peptide (VIP) is an abundant neurotransmitter in the lungs and other organs. Its discovery dates back to 1970. And VIP gains attention again due to the potential application in COVID-19 after a research wave in the 1980s and 1990s. The diverse biological impacts of VIP extend beyond its usage in COVID-19 treatment, encompassing its involvement in various pulmonary and systemic disorders. This review centers on the function of VIP in various lung diseases, such as pulmonary arterial hypertension, chronic obstructive pulmonary disease, asthma, cystic fibrosis, acute lung injury/acute respiratory distress syndrome, pulmonary fibrosis, and lung tumors. This review also outlines two main limitations of VIP as a potential medication and gathers information on extended-release formulations and VIP analogues.

Topics: Humans; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Vasoactive Intestinal Peptide

Although originally discovered because of their ability to affect hemodynamics, vasoactive peptides have been found to function in a variety of capacities including neurotransmission, endocrine functions, and the regulation of cell proliferation. A growing body of evidence describes the ability of vasoactive peptides to regulate cell death by apoptosis in either a positive or negative fashion depending on the peptide and the type of target cell. The available evidence to date is strongest for the peptides endothelin, angiotensin II, vasoactive intestinal peptide, atrial natriuretic peptide, and adrenomedullin. Each of these peptides is discussed, with specific regard to apoptosis, in terms of regulatory activity, target cell specificity, and potential role in pulmonary physiology.

Topics: Adrenomedullin; Angiotensin II; Animals; Apoptosis; Atrial Natriuretic Factor; Endothelin-1; Humans; Lung; Lung Diseases; Peptides; Vasoactive Intestinal Peptide

Topics: Animals; Endothelium, Vascular; Epithelium; Humans; Lung; Lung Diseases; Neuropeptides; Neurotransmitter Agents; Vasoactive Intestinal Peptide

The first bronchoactive (and vasoactive) peptide to be discovered in the lung was isolated and characterized in 1970 from an embryologically related organ, the small intestine. Since then, more than 20 additional peptides have been described in lung tissue and their biologic activities investigated. Many of these are neuropeptides acting as neurotransmitters or neuromodulators to influence airway, pulmonary vascular, and other functions. More neuropeptides are known to exist in the brain and peripheral nervous system; at least some of these are soon likely to be identified in the lung. With the accelerated pace of research, the coming few years should see an increasing definition of the role of neuropeptides in lung physiology and pathophysiology, as well as in improved management of certain respiratory disorders.

Topics: Animals; Autonomic Nervous System; Drug Interactions; Guinea Pigs; Lung Diseases; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Neuropeptides; Neurotransmitter Agents; Receptors, Neurotransmitter; Respiratory Physiological Phenomena; Respiratory System; Substance P; Vasoactive Intestinal Peptide

The present study was undertaken to develop a respirable sustained-release powder (RP) formulation of long-acting VIP derivative, [Arg(15, 20, 21), Leu(17)]-VIP-GRR (IK312532), using PLGA nanospheres (NS) with the aim of improving the duration of action. NS formulation of IK312532 (IK312532/NS) was prepared by an emulsion solvent diffusion method in oil, and a mixture of the IK312532/NS and erythritol was jet-milled and mixed with lactose carrier to obtain the IK312532/NS-RP. Physicochemical properties were characterized focusing on appearance, particle size, and drug release, and in vivo pharmacological effects were assessed in antigen-sensitized rats. The IK312532/NS with a diameter of 140 nm showed a biphasic release pattern in distilled water with ca. 20% initial burst for 30 min and a sustained slow release up to ca. 55% for 24h. Laser diffraction analysis demonstrated that IK312532/NS-RP had fine dispersibility and suitable particle size for inhalation. In antigen-sensitized rats, insufflated IK312532/NS-RP (10 μg of IK312532/rat) could suppress increases of granulocyte recruitment and myeloperoxidase in pulmonary tissue for up to 24h after antigen challenge, although IK312532-RP at the same dose was less effective with limited duration of action. From these findings, newly prepared IK312532/NS-RP might be of clinical importance in improving duration of action and medication compliance for treatment of airway inflammatory diseases.

Topics: Administration, Inhalation; Animals; Asthma; Bronchoalveolar Lavage Fluid; Delayed-Action Preparations; Disease Models, Animal; Granulocytes; Lung; Lung Diseases; Male; Nanospheres; Peroxidase; Pneumonia; Rats; Rats, Sprague-Dawley; Respiratory System; Vasoactive Intestinal Peptide

Cigarette smoke (CS) has been identified as a predominant causative factor for chronic obstructive pulmonary disease (COPD), so CS-exposed rodent model of COPD has drawn considerable interest and attention for fundamental study and drug discovery. In the present study, using experimental COPD model rats, the therapeutic potential of a newly prepared respirable powder (RP) formulation of a long-acting VIP derivative, [Arg(15,20,21), Leu(17)]-VIP-GRR (IK312532), was assessed with a focus on pro-inflammatory biomarkers, morphological and histochemical changes, and infiltrated cells in the respiratory system. CS exposure of rats for 11 days led to the marked infiltration of inflammatory cells, except for eosinophils, in bronchiolar epithelium, followed by goblet cell metaplasia and hyperplasia. However, inhalation of IK312532-RP (50μg/rat) in the CS-exposed rats resulted in 74 and 71% reductions of granulocyte recruitment in bronchoalveolar lavage fluids and lung tissues, respectively, with 68% decrease of goblet cells. Biomarker study demonstrated that the inhaled IK312532-RP could suppress the CS-evoked increase of myeloperoxidase in both plasma and lung by 87 and 70%, respectively, possibly leading to potent suppression of neutrophilic inflammatory symptoms. The results from TUNEL staining were indicative of apoptotic damage in respiratory tissues of the CS-exposed rats, and there appeared to be marked decrease of TUNEL-positive cells in the CS-exposed rat with inhaled IK312532-RP. The present findings suggest that an inhalable formulation of IK312532 might be efficacious as a therapy for COPD or other airway inflammatory diseases because of its potent immunomodulating activities.

Topics: Administration, Inhalation; Animals; Anti-Inflammatory Agents; Biomarkers; Eosinophil Peroxidase; Inflammation; Lung Diseases; Male; Neutrophils; Nicotiana; Peroxidase; Powders; Rats; Rats, Sprague-Dawley; Respiratory Mucosa; Smoke; Vasoactive Intestinal Peptide

Pulmonary hypertension (PH) leads to an increased right ventricular workload, cardiac failure and death. In idiopathic pulmonary arterial hypertension (PAH) the vasodilating vasoactive intestinal peptide (aviptadil) is deficient. The aim of the present study was to test the acute effects on haemodynamics and blood gases, and the safety, of a single dose of inhaled aviptadil in chronic PH. A total of 20 patients with PH (PAH in nine, PH in lung disease in eight and chronic thromboembolic PH in three) inhaled a single 100-microg dose of aviptadil during right-heart catheterisation. Haemodynamics and blood gases were measured. Aviptadil aerosol caused a small and temporary but significant selective pulmonary vasodilation, an improved stroke volume and mixed venous oxygen saturation. Overall, six patients experienced a pulmonary vascular resistance reduction of >20%. In patients with significant lung disease, aviptadil tended to improve oxygenation. The pulmonary vasodilating effect of aviptadil aerosol was modest and short-lived, did not cause any side-effects and led to a reduced workload of the right ventricle without affecting systemic blood pressure. Aviptadil inhalation tended to improve oxygenation in patients with significant lung disease. Further studies are needed to evaluate the full therapeutic potential of aviptadil aerosol, including higher doses and chronic treatment.

Topics: Adult; Aerosols; Aged; Blood Pressure; Drug Combinations; Female; Heart Failure; Heart Ventricles; Humans; Hypertension, Pulmonary; Lung Diseases; Male; Middle Aged; Oxygen; Phentolamine; Vasoactive Intestinal Peptide

To explore the nature of pathology of sluggishness of lung-defensive qi and to offer objective experimental indexes for weifen syndrome (defensive phase syndrome).. According to the completely random design, the plasma levels of vasoactive intestinal peptide (VIP) and thromboxane B2 (TX2) of 19 patients with weifen syndrome and 13 patients with qifen syndrome (qi phase syndrome) were detected by radioimmunoassay. The plasma levels of VIP and TX2 at different stages of weifen syndrome and qifen syndrome were observed.. The plasma levels of VIP in weifen syndrome and in the late stage of weifen syndrome increased greatly at different stages as compared to qifen syndrome and the blank group (P < 0.01), while the plasma level of TX2 of weifen syndrome was higher only at the late stage than the blank group and qifen syndrome (P < 0.01). As for the levels of VIP and TX2 in weifen syndrome with different internal organs infected, there was no significant difference (P > 0.05).. VIP may be an index reflecting the pathology of weifen syndrome, and it is one of the material foundations of sluggishness of lung-defensive qi, but it has nothing to do with the infected internal organs. The level of TX2 increases only after the fever of patients with weifen syndrome subsided, so it can not be the basis for diagnosis of the early stage of weifen syndrome. It doesn't increase in qifen syndrome either, the mechanism remains to be further studied.

Topics: Female; Humans; Lung Diseases; Male; Radioimmunoassay; Syndrome; Thromboxane B2; Vasoactive Intestinal Peptide

N-methyl-D-aspartate receptors, found throughout the mammalian brain, are a component of the major excitatory transmitter system. Strong evidence exists that N-methyl-D-aspartate receptors, by promoting excessive entry of Ca2+ into neurons, play a role in neuronal damage that follows head injury, strokes, and epileptic seizures, and is associated with degenerative diseases such as Alzheimer's disease. Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. We have investigated whether N-methyl-D-aspartate receptors exist in peripheral neurons, and, if so, whether their activation may result in tissue injury. We report that N-methyl-D-aspartate receptors exist in the lung, that their activation triggers acute injury, and that, as in toxicity to central neurons, this injury is associated with stimulation of nitric oxide synthesis, and can be attenuated by inhibition of this synthesis. Finally, vasoactive intestinal peptide, which protects the lung and heart against oxidant injury and promotes neuronal survival and differentiation also prevented N-methyl-D-aspartate lung injury, apparently by inhibiting a key neurotoxic action of nitric oxide, but not its production. The findings suggest that N-methyl-D-aspartate receptors exist in the peripheral nervous system and that activation of these receptors, resulting in damage to peripheral neurons, may be a novel mechanism of lung and other organ injury.

Topics: 2-Amino-5-phosphonovalerate; Animals; Cyclic GMP; Lung Diseases; N-Methylaspartate; Nitric Oxide; Organ Size; Peripheral Nervous System; Rats; Receptors, N-Methyl-D-Aspartate; Vasoactive Intestinal Peptide

Studies were conducted to compare the effect of native vasoactive intestinal peptide (VIP), Ro 25-1553 (a cyclic peptide analog of VIP) and salbutamol (a beta2-adrenoceptor agonist) on antigen-induced pathophysiological effects in the guinea pig. Ro 25-1553 and salbutamol (0.01-1.0 microM) prevented antigen-induced contractions of the guinea pig trachea in vitro with IC50 values of 0.07 and 0.05 microM, respectively. VIP (0.01-1.0 microM) had no effect on antigen-induced tracheal contractions. Aerosolized Ro 25-1553 and salbutamol were equipotent in preventing antigen-induced increases in guinea pig lung resistance (IC50 value = 0.0001%), whereas aerosolized VIP (0.1%) was ineffective. Ro 25-1553 (0.1-100 micrograms), instilled intratracheally 2 min before the antigen challenge of buffer-perfused lungs from sensitized guinea pigs, produced a dose-dependent inhibition of bronchoconstrictor, vasoconstrictor and edemagenic responses, whereas intratracheal VIP (100 micrograms) had no effect. Intratracheal salbutamol (0.1-100 micrograms) inhibited antigen-induced responses in a manner comparable to Ro 25-1553. Lung inflammation was assessed as leukocyte accumulation in bronchoalveolar lavage fluid after the antigen provocation. Aerosolized antigen-induced bronchoalveolar lavage eosinophilia (13-fold increase over saline controls) at 6 hr after challenge was prevented in a concentration-dependent manner by pretreatment with nebulized Ro 25-1553 and salbutamol, but not by pretreatment with native VIP. These results indicate that Ro 25-1553 suppresses various pathophysiological features associated with pulmonary anaphylaxis and asthma, including airway reactivity, edema formation and granulocyte accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Albuterol; Anaphylaxis; Animals; Antigens; Asthma; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Disease Models, Animal; Guinea Pigs; In Vitro Techniques; Lung Diseases; Male; Muscle Contraction; Muscle, Smooth; Peptides, Cyclic; Perfusion; Vasoactive Intestinal Peptide

We earlier showed that the neuropeptide vasoactive intestinal peptide (VIP) reduces or prevents acute injury produced in rat lungs by xanthine and xanthine oxidase. We have now examined whether VIP can protect against lung injury induced by paraquat, a prooxidant pesticide. Isolated guinea pig lungs were perfused for 60 min with Krebs-4% albumin and mechanically ventilated with 95% O2-5% CO2. Infusion of paraquat (100 mg/kg) into the pulmonary artery (n = 9 observations) increased peak airway pressure from 10.1 +/- 0.6 to 54.7 +/- 6.5 cmH2O, perfusion pressure from 8.0 +/- 0.5 to 14.9 +/- 3.0 cmH2O, wet-to-dry lung weight ratio to 7.17 +/- 0.37, and bronchoalveolar lavage protein content to 2.70 +/- 0.83 mg/ml (P < 0.01). Pretreatment with 1-3 micrograms.kg-1 x min-1 VIP markedly attenuated or prevented all abnormalities. Of the related peptides tested, helodermin was as effective as VIP, but secretin and glucagon were ineffective. The results demonstrate that VIP and helodermin protect perfused guinea pig lungs against paraquat-induced injury and support the view that VIP has antioxidant activity.

Topics: Animals; Body Water; Guinea Pigs; In Vitro Techniques; Intercellular Signaling Peptides and Proteins; Lung; Lung Diseases; Male; Paraquat; Peptides; Perfusion; Permeability; Pressure; Prostaglandin-Endoperoxide Synthases; Proteins; Vasoactive Intestinal Peptide

The neuropeptide gastrin releasing peptide (GRP) is present in the lung, and functions as a modulator of tissue growth and repair in fibrotic processes, or as a modulator of cell movement and differentiation in various inflammatory processes, including granulomatous ones. In idiopathic pulmonary fibrosis (IPF), changes in the bronchoalveolar lavage (BAL) content of GRP can be expected. We measured GRP-like immunoreactive substances (GRP-IS) and another neuropeptide, vasoactive intestinal peptide (VIP)-IS in BAL by enzyme immunoassay. Our results showed a decrease in BAL GRP-IS in patients with IPF (26.5 +/- 5.5 pg.mg-1 protein) and sarcoidosis (35.9 +/- 9.2 pg.mg-1), compared to healthy nonsmokers (63.4 +/- 9.0 pg.mg-1). When data were expressed as pg.ml-1 BAL fluid recovered, a decrease was only seen in IPF, not in sarcoidosis. The levels of VIP-IS in BAL were not different between the groups studied. Increased protein levels in BAL had no correlation with the levels of GRP-IS or VIP-IS in BAL. Furthermore, BAL neutrophil percentages had no correlation with the levels of GRP-IS in BAL of patients with IPF. Using reversed phase high performance liquid chromatography (HPLC), several kinds of GRP-IS were detected in BAL. These findings suggest that the decreased level of GRP-IS in BAL may reflect a loss of GRP-producing cells due to chronic lung injury and fibrosis in patients with IPF.

Topics: Adult; Bronchoalveolar Lavage Fluid; Chromatography, High Pressure Liquid; Female; Gastrin-Releasing Peptide; Gastrointestinal Hormones; Humans; Immunoenzyme Techniques; Lung Diseases; Male; Middle Aged; Peptides; Pulmonary Fibrosis; Sarcoidosis; Smoking; Vasoactive Intestinal Peptide