Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inhalation of platelet activating factor (PAF) produces bronchoconstriction in normal and asthmatic subjects. To identify the mechanism by which PAF-induced bronchoconstriction occurs in humans, bronchoprovocation testing was performed in 7 subjects (3 normal, 4 with mild asthma) after pretreatment with phosphate-buffered saline (PBS), atropine, chlorpheniramine, or indomethacin. We determined the nebulizer concentration of PAF which reduced specific airway conductance (SGaw) 35% (PC35 SGaw) and the slope of the PAF dose-response curve. Atropine produced baseline bronchodilatation (SGaw increased 50%), while chlorpheniramine and indomethacin had no effect on baseline pulmonary function. Atropine increased airway responsiveness to PAF: the PC35 SGaw decreased 40% (p less than 0.05) and the slope of the PAF dose-response curve increased 86% (p less than 0.05). In contrast, chlorpheniramine inhibited the airway response to PAF: the PC35 SGaw increased 87% (p less than 0.05), while the slope of the PAF dose-response curve decreased an insignificant 37%. Indomethacin did not affect either measurement. Chlorpheniramine also prevented the PAF-induced facial flushing and feeling of warmth; atropine and indomethacin did not. These results suggest that PAF-induced bronchoconstriction in humans is mediated at least in part by histamine release, not by cholinergic or cyclooxygenase-dependent mechanisms. Other indirect effects, such as the release of sulfidopeptide leukotrienes, or a direct effect on airway smooth muscle may also contribute to PAF-induced bronchoconstriction. Why atropine heightened the airway response to PAF is unclear.
 ...
PMID:Mechanism of platelet activating factor-induced bronchoconstriction in humans. 319

Cumulative addition of atropine to the organ bath containing endothelium-intact (+E) rat aorta, which was precontracted with phenylephrine (PE, 1 microM) and subsequently relaxed with carbachol (1 microM), caused biphasic changes in the vascular contractility of +E rat aortic rings. Low concentrations of atropine (10 nM-1.0 microM) caused progressive restoration of contraction to PE; whereas at higher concentrations (1-100 microM), atropine caused progressive relaxation. Atropine-induced aortic relaxation was significantly inhibited upon endothelium removal by either rubbing or saponin treatment, but considerable relaxation still persisted in the range of 30-100 microM atropine. Similar findings were also obtained when the nitric oxide (NO) generation was inhibited with 300 microM NO synthase inhibitor, L-NAME. Atropine-induced relaxation was also observed when 5-hydroxytryptamine (5-HT) was used as the agonist and the atropine-relaxation was more potent at lower concentrations of PE and 5-HT. However, atropine had no effect on the contraction elicited by KCl or prostaglandin F(2 alpha). Also, atropine-induced relaxation was not affected by indomethacin (1-10 microM), nicotine (10-100 microM) or hexamethonium (30 microM). Pretreatment of +E aorta with tetraethylammonia (TEA, 3-10 mM) or 4-aminopyridine (4-AP, 1-3 mM) showed prominent inhibitory effect on atropine-induced relaxation; on the other hand, preincubation with glibenclamide (1-10 microM), BaCl(2) (1-30 microM) or 2 microM charybdotoxin and apamin, had little effect on the relaxation induced by atropine. When added to tissues after relaxation to atropine, TEA and 4-AP concentration-dependently reversed the relaxation in -E aorta, whereas in +E aorta, TEA up to 30 mM and 4-AP up to 10 mM only partially affected atropine-induced relaxation. Although TEA and 4-AP potentiated the PE-contraction, such potentiation is unlikely to contribute to the change in sensitivity to atropine-induced relaxation, since in the presence of 15 mM KCl, which also potentiated PE-contraction to a comparable extent, the atropine-relaxation remains unchanged. Scopolamine also acts like atropine, except that the effect of scopolamine was smaller than that of atropine and is primarily endothelium-dependent. Atropine-induced relaxation also occurs in medium artery (renal artery) and small muscular artery (mesenteric artery). In conclusion, atropine-relaxation is mediated in part via voltage-dependent K(+) channels in both smooth muscle and endothelium and forms the mechanistic basis for the observed vasodilation, reduced blood pressure and facial flushing following atropine overdose.
 ...
PMID:In vitro relaxation of vascular smooth muscle by atropine: involvement of K+ channels and endothelium. 1280 79