Synergistic effect of nitric oxide and vasoactive intestinal peptide on bronchoprotection against histamine in anesthetized guinea pigs.

Abstract

Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are considered to be nonadrenergic, noncholinergic (NANC) inhibitory neurostransmitters in the airways. It seems likely that these neurotransmitters may be coreleased and act as functional antagonists against bronchoconstrictor stimuli. In the present study, we examined the synergistic effect of NO and VIP on bronchoprotection against histamine in anesthetized guinea pigs. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP) significantly inhibited histamine-induced bronchoconstriction in a dose-dependent manner. VIP also inhibited histamine-induced bronchoconstriction in a dose-dependent manner, but this bronchoprotective effect was short-lived. Additionally, VIP (10(-9) M) had no significant bronchoprotective effect, but a subthreshold dose of SNAP (10(-7) M) significantly potentiated VIP (10(-9) M)-induced bronchoprotection against histamine. Moreover, SNAP (10(-7) M) significantly enhanced VIP (10(-7) M)-induced bronchoprotection for a longer period of time. On the other hand, VIP (10(-9) M) also significantly potentiated SNAP-induced bronchoprotection against histamine. In conclusion, combination therapy with NO donor and VIP receptor agonist may have important advantages in the treatment of bronchial asthma, and both NO and VIP may contribute in complementary fashion to the NANC-induced relaxant response in guinea pig airways.

Additive role of tiotropium in severe asthmatics and Arg16Gly in ADRB2 as a potential marker to predict response

“…Cholinergic tone is thought to be increased in asthma by several mechanisms, i.e., increased afferent stimulation by inflammation (27), abnormal muscarinic receptor expression (28), increased release of acetylcholine from cholinergic nerve ending (29), and decreased levels of neuromodulators that attenuate cholinergic neurotransmission (30). Nevertheless, the use of anticholinergics in asthma has been justified only in asthma exacerbations (3).…”

Vasoactive intestinal peptide regulates sinonasal mucociliary clearance and synergizes with histamine in stimulating sinonasal fluid secretion

“…It is thought that VIP activates receptor‐linked Gα s and downstream adenylyl and/or guanylyl cyclase activation, resulting in stimulation of cyclic adenosine monophosphate (cAMP)‐dependent protein kinase A (PKA) and/or cGMP‐dependent protein kinase G (PKG) (24–26). However, it has been suggested that half of the vasodilatory effects of VIP are mediated by nitric oxide (NO) signaling (27–29). VIP also stimulates intracellular Ca 2+ signaling in some cells (3, 5, 6), including human nasal submucosal gland serous cells, where VIP also enhances the magnitude of cholinergic‐induced Ca 2+ signals (3).…”

Administration of domestic bronchodilators in patients with bronchial asthma

“…Подчеркивая значение этого меха низма бронхоконстрикции, Г.Б.Федосеев выделяет даже "холинергический вариант БА", описывая его клинические особенности [11]. Ряд механизмов, та ких как усиление стимуляции афферентных рецеп торов медиаторами воспаления [12], повышенное высвобождение ацетилхолина из холинергических нервных окончаний [13], ненормальная экспрессия мускариновых рецепторов посредством увеличения количества М3 рецепторов или уменьшения М2 ре цепторов [14], снижение уровня нейромодуляторов (вазоактивного кишечного пептида, оксида азота), тормозящих нейротрансмиссию [15], приводят к по вышению холинергического тонуса при БА, что оправдывает назначение в качестве бронхолитичес кой терапии антихолинергических препаратов. Кро ме того, было обнаружено, что у больных с генотипом Arg/Arg бронходилатирующий эффект ипратропия даже более выражен, чем сальбутамола [16].…”