Effect of salbutamol on pulmonary responsiveness in chronic pulmonary allergic inflammation in guinea pigs

Abstract

Beta-2-agonists have been widely used by asthmatic subjects to relieve their obstructive symptoms. However, there are reports that continuous use could lead to loss of bronchial protection and exacerbation of asthma symptoms. We evaluated the effect of two regimens of salbutamol administration (twice and five times a week) in a model of chronic airway inflammation in male Hartley guinea pigs (protocol starting weight: 286 ± 30 g) induced by repeated exposures to aerosols of ovalbumin (OVA). After sensitization, guinea pigs were exposed to aerosols of 0.1 mg/ml salbutamol solution twice a week (OVA + S2x, N = 7) or five times a week (OVA + S5x, N = 8). We studied allergenspecific (OVA inhalation time) and -nonspecific (response to methacholine) respiratory system responsiveness. Seventy-two hours after the last OVA challenge, guinea pigs were anesthetized and tracheostomized, respiratory system resistance and elastance were measured and a dose-response curve to inhaled methacholine chloride was obtained. Specific IgG 1 was also quantified by the passive cutaneous anaphylactic technique. OVA-sensitized guinea pigs (N = 8) showed reduction of the time of OVA exposure before the onset of respiratory distress, at the 5th, 6th and 7th exposures (P < 0.001). The OVA + S2x group (but not the OVA + S5x group) showed a significant increase in OVA inhalation time. There were no significant differences in pulmonary responsiveness to methacholine among the experimental groups. OVA + S2x (but not OVA + S5x) animals showed a decrease in the levels of IgG 1 -specific anaphylactic antibodies compared to the OVA group (P < 0.05). Our results suggest that, in this experimental model, frequent administration of ß 2 -agonists results in a loss of some of their protective effects against the allergen.

In Vitro Study of the Bronchorelaxation Effect of Coptosapelta Flavescens Korth. Root’s Extract and Fractions

“…MLCP activation will prevent the binding of actin and myosin which leads to smooth muscle relaxation. The decrease in intracellular Ca 2+ concentrations also causes a reduction in Ca-calmodulin binding such that contraction does not occur [11,12,13]. Other mechanisms that can affect bronchorelaxation are non-adrenergic non-cholinergic receptor pathway inhibitor, calcium channel antagonist, potassium channel activator, and epithelium-derived relaxing factors such as nitrite oxide and prostaglandin E2 [13,14].…”

Spatial Distribution of (R)-salbutamol in Rat Brain Following Nasal and Intravenous Administration Using DESI-MS

“…Salbutamol is a racemic mixture of (S)-salbutamol and (R)-salbutamol and (R)-salbutamol is the eutomer (structure shown in Figure 1) [4]. Binding of (R)-salbutamol and S-salbutamol with β2-receptor has opposite effects on calcium concentration, bronchoconstriction, airway responsiveness and eosinophils [5][6][7][8]. Moreover, (R)-salbutamol can activate adenylate cyclase and increase the content of cAMP in cells, and increased cAMP will inhibit the release of inflammatory factors produced by mast cells and eosinophils [9].…”