Nitric oxide pathway-mediated relaxant effect of PPAR (Peracisome proliferator activated receptor)-Gamma agonist in the guinea-pig isolated trachea.

Objectives: This study focuses on the role of the mediator of smooth muscles i.e. nitric oxide in the effect of rosiglitazone on the relaxation of contractions in guinea pig trachea induced by histamine. Study Design: Experimental Study. Setting: Department of Pharmacology, Army Medical College, Rawalpindi. Period: 1st December 2018 till 14th December 2018. Material & Methods: The activity of the trachealis mucle of the guinea pigs was noted by the use of oxygenated solution of Krebs-Henseleit. The contractions were noted with rosiglitazone alone as well as in presence of an ester of L-nitro-arginine-methyl, which can antagonize the activity of NO. The activity was measured by the use of an isometric force displacement transducer and was then recorded on an oscillograph with four channels. Results: The ester L-nitro-arginine-methyl was able to reduce the relaxant effect of rosiglitazone on the contractions induced by histamine. Conclusion: It can be suggested that the relaxation induced by rosiglitazone is mediated in part through NO.

RELAXATION ACTIVITY OF TETANUS (LEEA AEQUATA L.) LEAF ETHANOLIC EXTRACT ON GUINEA PIG ISOLATED TRACHEA

Objective: The aim of this study is to determine the relaxation activity of the ethanolic extract of tetanus leaf (EETL) against contracting isolated guinea pig trachea induced by acetylcholine.Methods: Isolated trachea was equilibrated for 45 min until a stable condition in the Creb’s solution with a temperature of 37°C aerated with carbogen gas (O2:CO2=95%:5%). Test of the relaxation effect conducted after guinea pig trachea contracted with maximum acetylcholine concentration (EC80: 2.0449×10–3 mol) and then a cumulative with concentration of EETL (0.5 mg/mL–4 mg/mL) and concentration of atropine sulfate (6.95×10-6 mg/mL–2.08×10–2 mg/mL).Results: The results showed that EETL could lower the contraction smooth muscle of guinea pig trachea induced by acetylcholine. EETL at a concentration of 3.5 mg/mL had the ability to relax the muscle. It was not significantly different compared to that of atropine sulfate 6.95×10-3 mg/ mL (p>0.005).Conclusion: EETL has a relaxation effect on smooth muscle of guinea pig isolated trachea.

Modified method for bronchial suture by Ramirez Gama compared to separate stitches suture: experimental study

OBJECTIVE: To experimentally compare two classic techniques described for manual suture of the bronchial stump. METHODS: We used organs of pigs, with isolated trachea and lungs, preserved by refrigeration. We dissected 30 bronchi, which were divided into three groups of ten bronchi each, of 3mm, 5mm, and 7mm, respectively. In each, we performed the suture with simple, separated, extramucosal stitches in five other bronchi, and the technique proposed by Ramirez and modified by Santos et al in the other five. Once the sutures were finished, the anastomoses were tested using compressed air ventilation, applying an endotracheal pressure of 20mmHg. RESULTS: the Ramirez Gama suture was more effective in the bronchi of 3, 5 and 7 mm, and there was no air leak even after subjecting them to a tracheal pressure of 20mmHg. The simple interrupted sutures were less effective, with extravasation in six of the 15 tested bronchi, especially in the angles of the sutures. These figures were not significant (p = 0.08). CONCLUSION: manual sutures of the bronchial stumps were more effective when the modified Ramirez Gama suture was used in the caliber bronchi arms when tested with increased endotracheal pressure.

Androgens are bronchoactive drugs that act by relaxing airway smooth muscle and preventing bronchospasm

Changes in the androgen levels in asthmatic men may be associated with the severity of asthma. Androgens induce a nongenomic relaxation in airway smooth muscle, but the underlying mechanisms remain unclear. The aim of this study was to investigate the potential bronchorelaxing action of testosterone (TES) and its metabolites (5α- and 5β-dihydrotestosterone (DHT). A preventive effect on ovalbumin (OVA)-induced bronchospasm was observed in sensitized guinea pigs for each androgen. Androgens were studied in response to bronchoconstrictors: carbachol (CCh) and KCl in isolated trachea rings with and without epithelium from non-sensitized and sensitized animals as well as on OVA-induced contraction. Androgens concentration-dependently abolished the contraction in response to CCh, KCl, and OVA. There were significant differences in the sensitivity to the relaxation induced by each androgen. 5β-DHT was more potent for relaxing KCl-induced contraction, while TES and 5α-DHT were more potent for CCh- and OVA-induced contraction. No differences were found in preparations with and without epithelium or in the presence of a nitric oxide (NO) synthase inhibitor or an inhibitor of K+channels. These data indicate the absence of involvement of the epithelium-, NO- and K+channels-dependent pathway in androgen-induced relaxation. However, in dissociated tracheal myocytes loaded with the calcium-binding fluorescent dye Fura -2, physiological concentrations of androgens decreased the KCl-induced [Ca2+]iincrement. 5β-DHT was the most potent at decreasing KCl-induced [Ca2+]iincrement and preventing bronchospasm. We suggest that androgen-induced brochorelaxation was mediated via decreased Ca2+influx through L-type Ca2+channels but additional Ca2+entry blockade may be involved. Molecular changes in androgen structure may determine its preferential site of action.

Butylidenephthalide Blocks Potassium Channels and Enhances Basal Tension in Isolated Guinea-Pig Trachea

Butylidenephthalide (Bdph, 30~300 μM), a constituent ofLigusticum chuanxiongHort., significantly enhanced tension in isolated guinea-pig trachea. In this study, we investigate the mechanism(s) of Bdph-induced contraction in the tissue. Isolated trachea was bathed in 5 mL of Krebs solution containing indomethacin (3 μM), and its tension changes were isometrically recorded. Cromakalim (3 μM), an ATP-dependent K+channel opener, significantly antagonized the Bdph-induced enhancement of baseline tension. Bdph (300 μM) also significantly antagonized cromakalim-induced relaxation. Bdph (300 μM) did not significantly influence the antagonistic effects of glibenclamide (GBC, 1 μM) and tetraethylammonium (TEA, 8 mM) against the cromakalim-induced relaxation. However, Bdph (300 μM) and 4-aminopiridine (4-AP, 5 mM), a blocker of Kv1 family of K+channels, in combination significantly rightward shifted the log concentration-relaxation curve of cromakalim. The antagonistic effect of the combination almost equals the sum of the individual effects of Bdph and 4-AP, suggesting that the antagonistic mechanism of Bdph may be similar to that of 4-AP. All calcium channel blockers influenced neither the baseline tension nor antagonistic effect of Bdph against cromakalim. In conclusion, Bdph may be similar to 4-AP, a blocker of Kv1 family of K+channels, to enhance the baseline tension of guinea-pig trachea.