Pharmacological effects of gemfibrozil on some isolated smooth muscle preparations of experimental animals

Background: Gemfibrozil is a member of fibrates (gemfibrozil, fenofibrate, ceprofibrate, and benzafibrate) which is employed for treatment of dyslipidemia particularly hypertriglyceridemiae through its action on peroxisome proliflator activated receptors (PPAR-). Objective: The aim of this work was to study the site of action and pharmacololgical effects of different doses of gemfibrozil on some isolated smooth muscles preparations of experimental animals. Materials and Methods: The experiments were conducted on isolated jejunum of rabbits, isolated spiral tracheal and urinary bladder strips of guinea pigs. Results: I- On isolated rabbit jejunum, gemfibrozil produced a dose-dependent reduction on the amplitude of jejunal contractions. The inhibitory effect of gemfibrozil was not abolished after complete blockade of alpha and beta adrenergic receptors, while it was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. On the other hand the stimulatory effects of nicotine small dose, acetylcholine, calcium gluconate, histamine and serotonin were not abolished after administration of gemfibrozil. II- On isolated tracheal spiral strips of ginea pigs, gemfibrozil produced a dose- dependent relaxation on the basal tone and a dose-dependent reduction on the amplitude of acetylcholine-induced tracheal contractions of the tracheal strips. The inhibitory effect of gemfibrozil was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. Gemfibrozil completely abolished also serotonin-induced contraction, while it has no effect on histamine or calcium-induced tracheal contractions. III- On isolated urinary bladder strips of guinea pigs, gemfibrozil produced a dose-dependent reduction on the amplitude of urinary bladder contractions. The inhibitory effect of gemfibrozil was not abolished after complete blockade of beta adrenergic receptors, while it was completely abolished after inhibition of nitric oxide synthase by N-methyl L-arginine. On the other hand the stimulatory effects of acetylcholine and serotonin were not abolished after administration of gemfibrozil. Conclusion: Gemfibrozil (antidyslipidemic, PPAR- agonist) reduced jejunal and urinary bladder contractions and has a relaxant effect on tracheal basal tone. So it has a beneficial effect in obstructive airway diseases and cases of urgency and frequency of micturation and urinary incontinence. However, it may be used cauciously in cases of ,GIT disturbances as constipation and prostatic hypertrophy

Modulation in airway smooth muscle reactivity and improvement in lung function of cigarette smokers and passive non-smokers following garcinia kola treatment

Inhalation of tobacco smoke is a major risk factor for the development of airway hyperreactivity (AHR) in non-cigarette smokers and increase respiratory distress in smokers. Garcinia kola has been linked to smooth muscle relaxation and may ameliorate obstruction and resistance to airflow. This study examined the effect of Garcinia kola on airflow and reactivity of the airway smooth muscles (ASM) of asymptomatic regular cigarette smokers (CS) and passive non-smokers (PNS) following 10 minutes cigarette smoking and exposure to cigarette smoke. Sixty apparently healthy male undergraduates comprising cigarette smokers and non-smokers volunteered as subjects. Changes in peak expiratory flow rate (PEFR) in L/min in CS and PNS was measured with Spirometer before and after 10 minutes of smoking and/or exposure to cigarette smoke. Thereafter, half the population of CS and PNS were given G. kola (200 mg/kg body weight) and PEFR measured at intervals of 30 minutes for a maximum of 90 minutes. Peak expiratory flow rate significantly decreased (p < 0.05) following 10 minutes of smoking and exposure to smoke in both CS and PNS, however, G. kola ingestion marginally increased PEFR values significantly at 30, 60 and 90 minutes intervals. Comparatively, increase in PEFR was greater in PNS than in CS (P < 0.05) treated with G. kola and climaxed at 60 minutes. Conclusively, cigarette smoking and exposure to cigarette smoke compromise lung function with a decrease in peak expiratory flow rate. G. kola treatment significantly reversed this trend, cleared the airways, enhanced airflow and improved lung function

Effect of Chronic High Altitude Hypoxia on Foetal and Maternal Juxta-Alveolar Distal Pulmonary Smooth Muscle Cells Actin and Calponin Organisation and Growth Profiles

BACKGROUND: The effect of chronic high altitude hypoxia (CHAH) in the juxta-alveolar region near the air-blood interface is unknown because of the experimental inaccessibility of this region. OBJECTIVE: To examine primary cultures of digested juxtaalveolar smooth muscle cells for hypoxia-induced changes. METHODS: Smooth Muscle Cells (SMCs) obtained by dispase digestion of the extreme lung parenchyma were used to study the effect of CHAH in the juxta-alveolar region and foetal and maternal cells were compared. Pulmonary venous SMCs were also obtained from dissected 5th to 7th generation levels pulmonary veins (0.5 mm). Fluorescence tagged antibodies against alpha smooth muscle actin (alpha SMA) and calponin respectively were used as markers to identify cellular structural differences by routine immunohistochemistry. Comparison of the functional integrity of the cells was made using their growth profiles obtained by radiolabeled thymidine incorporation and liquid scintillation counting. RESULTS: Marked differences were seen in juxta-alveolar SMCs obtained by digestion of extreme lung parenchyma of hypoxic sheep. Hypoxic adult sheep cells showed increased filamentation. Hypoxic foetal sheep cells showed internal restructuring and disorganization of both alpha-SMA and calponin filaments. The growth profiles of juxta-alveolar SMCs showed that the hypoxia-affected cells of both the foetus and adult sheep had a fast initial growth rate peaking at 48h while their normoxic equivalents had a steadier growth rate peaking at 72h. Hypoxia-affected cells showed contact inhibition at ~50subconfluence and apoptosis by 48h. CONCLUSION: Chronic high altitude hypoxia causes both phenotypical and functional changes in pulmonary smooth muscle cells near the air/blood interface