Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Horses suffer from a respiratory condition, similar to human allergic asthma, that is characterized by severe dyspnea, wheezing, coughing, and mucus production. Mediator substances released during the allergic reaction may contract airways and pulmonary vasculature. Nothing is known of the effects of autacoids and other vasoactive substances on equine pulmonary vessels. Therefore, spiral strips of equine pulmonary vein were prepared in vitro and the effects of histamine (H), 5-hydroxytryptamine (5HT), bradykinin (BK), carbachol (Carb), and phenylephrine (phen) were studied. The order of contractile effectiveness for the agonists on the vein was found to be 5HT greater than H greater than Bk greater than Phen greater than Carb, although H consistently produced the greatest maximal effects. H1-receptors appeared to mediate H contractions while H2-receptors had no measurable effect. 5HT responses were mediated directly by 'D-type' smooth muscle receptors. Bk produced contractions but of a lesser magnitude than either H or 5HT. Varying degrees of tachyphylaxis were observed for each agent. alpha-Adrenergic receptor stimulation by Phen initiated low-magnitude contractions whereas Carb exhibited virtually no activity on the pulmonary vein. Contractile responses of pulmonary veins to various spasmogens may contribute to the equine asthmatic response by raising vascular hydrostatic pressure, thereby enhancing edema formation.
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PMID:Pharmacological studies on the pulmonary vein of the horse. I. Effects of selected spasmogens. 3 May 26

1. The present study was performed in anaesthetized, artificially ventilated, open-chested rabbits to examine whether (a) the rapidly adapting receptors of the airways were stimulated by exogenously administered bradykinin, and (b) if this sensitivity could be enhanced by the angiotensin-converting-enzyme inhibitor, enalapril. 2. Rapidly adapting receptor activity (n = 8) was recorded from the cervical vagus. Bradykinin was injected intravenously (0.25-1.0 microgram/kg) and a dose-response curve relating receptor activity to bradykinin was elicited. In the control state, the threshold dose of bradykinin required for stimulation of rapidly adapting receptors was 0.53 +/- 0.11 microgram/kg. Five minutes after the administration of enalapril maleate (2 mg intravenously), the dose-response curve was shifted to the left significantly (P < 0.01). 3. In seven other rapidly adapting receptors, enalapril (2 mg) increased the resting activity significantly (P < 0.05) over a period of 60 min. This increase was significantly different from the spontaneous variation in neural activity of rapidly adapting receptors (n = 7) recorded over a period of 60 min. 4. Bradykinin either alone (0.25-1.0 microgram/kg) or in the presence of enalapril did not stimulate the slowly adapting receptors (n = 5) of the airways. 5. These results show that (a) exogenous bradykinin stimulates the rapidly adapting receptors, (b) the sensitivity of rapidly adapting receptors to bradykinin is enhanced by enalapril and (c) enalapril increases the resting activity of rapidly adapting receptors. It is suggested that the cough reported after the administration of enalapril may be due to stimulation of rapidly adapting receptors of the airways.
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PMID:Responses of airway rapidly adapting receptors to bradykinin before and after administration of enalapril in rabbits. 133 Apr 1

Axon reflex mechanisms may be involved in the pathogenesis of asthma, but there has been no direct evidence that endogenous tachykinins cause bronchoconstriction in asthmatic subjects. We have studied the effect of a tachykinin receptor antagonist (FK-224) on bronchoconstriction induced by inhalation of bradykinin in asthmatic patients. In a double-blind, placebo-controlled, crossover trial, ten subjects with stable asthma were given FK-224 (4 mg) or placebo by inhalation 20 min before challenge with bradykinin (0-1250 micrograms/ml, five breaths of each concentration) given with 5 min intervals. Bradykinin caused dose-dependent bronchoconstriction in all subjects. FK-224 significantly opposed the bronchoconstrictor effect; the geometric mean of the cumulative concentration required to elicit a 35% fall in specific airway conductance was 5.3 micrograms/ml after placebo and 40 micrograms/ml after FK-224 (p < 0.001). Inhalation of bradykinin caused coughing in three subjects, which was inhibited by FK-224 in all three. Antagonism of the tachykinin receptor by FK-224 greatly inhibited both bronchoconstriction and coughing induced by bradykinin in asthmatic patients, suggesting that tachykinin release from the airway sensory nerves is involved in responses to bradykinin. Tachykinin receptor antagonists may be useful in the treatment of asthma.
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PMID:Protection against bradykinin-induced bronchoconstriction in asthmatic patients by neurokinin receptor antagonist. 135 19

Bradykinin (BK) has several effects on airway function which may be relevant in obstructive airways disease. These effects are mediated via B2-receptors. BK is a potent bronchoconstrictor in animals and humans in vivo. Bradykinin contracts airway smooth muscle, is a potent bronchial vasodilator, increases microvascular leakage, stimulates epithelial cells to release bronchodilators and stimulates mucus secretion. Perhaps its most important action is the activation of sensory nerves in airways, leading to reflex bronchoconstriction, coughing and neurogenic inflammation through the release of neuropeptides from sensory nerves.
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PMID:Effect of bradykinin on airway function. 146 77

Cough induced by ACE-inhibitors may be related to bronchial hyperreactivity and/or to an accumulation of kinins. In a placebo-controlled, double-blind randomized study in asthmatic and hypertensive patients lung function and bronchial reactivity to histamine and bradykinin remained unaltered although in hypertensive patients with cough, reactivity to histamine tended to be more pronounced and bronchial hyperreactivity to be more frequent than in those without cough. The findings do not support a major role of kinins in ACE inhibitor-induced cough.
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PMID:Cough induced by ACE-inhibitors. A kinin related phenomenon? 146 82

Dry cough is one of the most common side-effects of angiotensin converting enzyme inhibitors. The mechanism of cough induced by ACE inhibitors is not completely understood and may be related to bronchial hyperreactivity and/or an accumulation of kinins. In a placebo-controlled, double-blind randomised study, the effect of captopril on lung function and bronchial reactivity to histamine and bradykinin was investigated in eight asthmatic and 12 hypertensive patients (six with and six without cough during previous ACE inhibition). Lung function did not change in any patient after a single (25 mg) or short-term (2 x 25 mg for two weeks) administration of captopril. Bronchial reactivity to histamine and bradykinin remained unaltered in all groups. In hypertensive patients with cough, reactivity to histamine tended to be more pronounced and bronchial hyperreactivity to be more frequent than in those without cough. In conclusion, the present results do not support a major role for kinins in cough induced by ACE inhibition. On the other hand, bronchial hyperreactivity may be important in some patients. Additionally, these results demonstrate that treatment with ACE inhibitors is safe in most patients with bronchial asthma.
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PMID:Airway responsiveness and cough induced by angiotensin converting enzyme inhibition. 146 96

Imbalance between peptides such as substance P and bradykinin, and related enzymes degrading these peptides may cause the development of cough in various pathological conditions. On the other hand, lack of cough reflex may cause aspiration pneumonia. Down and up regulation by peptides may be useful for treatment of cough and prevention of aspiration pneumonia.
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PMID:[Cough reflex in respiratory disease]. 169 91

It has been proposed that angiotensin converting enzyme (ACE) may play a part in the metabolism of substance P. Reduced metabolism following treatment with ACE inhibitors may cause accumulation of substance P to produce the adverse effect of cough. It has been shown in this study that, in contrast to angiotensin I and bradykinin, inhibition of local vascular ACE does not interfere with the vascular effects of substance P on forearm resistance vessels when this peptide is infused into the brachial artery of normal volunteers. These results suggest that endothelial ACE plays little part in the metabolism of intravascular substance P.
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PMID:The effect of local converting enzyme inhibition on the dilator response to substance P in the human forearm. 169 17

1. The effects of intravenous captopril and enalaprilic acid on the increase in pulmonary inflation pressure induced by different bronchoconstrictor agents were evaluated in the anaesthetized guinea-pig. 2. Captopril and enalaprilic acid (1.6-200 micrograms kg-1) enhanced dose-dependently the bronchoconstriction (BC) induced by substance P. The threshold effective dose was 1.6 micrograms kg-1 and maximal potentiation over the control response was more than 400% for both agents. Enalaprilic acid was also assayed for serum and lung angiotensin converting enzyme (ACE) inhibition in anaesthetized guinea-pigs. This drug produced a dose-dependent inhibition of ACE in both tissues, with ED50 s of 7.6 and 9.4 micrograms kg-1, respectively: this inhibitory activity was positively correlated to substance P potentiation. 3. Captopril (8-1000 micrograms kg-1) enhanced dose-dependently the BC induced by capsaicin. The threshold effective dose was 40 micrograms kg-1 and maximal potentiation about 90%. 4. Captopril (200-1000 micrograms kg-1) did not affect BC induced by bradykinin. However, this response was markedly enhanced (about 200%) by captopril 200 micrograms kg-1 in propranolol-pretreated animals. 5. Captopril and enalaprilic acid (200-1000 micrograms kg-1) slightly (20-40%) but significantly enhanced the BC induced by 5-hydroxytryptamine. However, this response was potentiated to the same extent by a dose of prazosin, which produced a degree of hypotension similar to that observed after administration of the ACE inhibitors. 6. In conclusion, ACE inhibitors potentiate the BC induced by substance P and, to a minor extent, that induced by capsaicin in the anaesthetized guinea-pig. Potentiation of substance P is well correlated with ACE inhibition in guinea-pig serum and lungs. These experimental results may offer a mechanistic interpretation of cough and bronchial hyperreactivity observed in patients receiving treatment with ACE inhibitors.
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PMID:Angiotensin converting enzyme inhibitors potentiate the bronchoconstriction induced by substance P in the guinea-pig. 169 96

In the present study we evaluated the effects of ruthenium red, a blocker of transmembrane Ca2+ fluxes, on bronchoconstriction and the release of calcitonin gene-related peptide-like immunoreactivity induced by different stimuli in the isolated perfused guinea-pig lung. Vagal stimulation (1 Hz, 1 min), capsaicin (10(-8) M, 10(-6) M), resiniferatoxin (3 x 10(-10) M), nicotine (10(-4) M), bradykinin (5 x 10(-6) M) and histamine (10(-5) M) evoked bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity overflow. Ruthenium red (5 x 10(-6) M) almost completely inhibited the bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity overflow induced by capsaicin and resiniferatoxin but did not influence the effects induced by vagal nerve stimulation, nicotine, bradykinin or histamine. The 20-deacetylated derivative of resiniferatoxin (ROPA), which lacks the homovanillyl ester group, did not evoke release or bronchoconstriction. Ruthenium red (3 x 10(-4) M) aerosol attenuated the cough induced by nebulized citric acid in conscious guinea-pigs. Citric acid-induced coughing is mediated via capsaicin-sensitive neurons. However, cigarette smoke-induced coughing, which involves capsaicin-resistant mechanisms, was not affected by ruthenium red. In conclusion, ruthenium red selectively inhibits the capsaicin, resiniferatoxin and citric acid-induced excitation of the sensory nerves as revealed by calcitonin gene-related peptide-like immunoreactivity release, bronchoconstriction and coughing, suggesting that these agents share a common mechanism of action.
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PMID:Selectivity of ruthenium red in inhibiting bronchoconstriction and CGRP release induced by afferent C-fibre activation in the guinea-pig lung. 171 14


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