Journal of Smooth Muscle Research
Search
OR
Browse
Search
Volume 46 , Issue 3
Showing 1-4 articles out of 4 articles from the selected issue
    • |<
    • <
    • 1
    • >
    • >|
Original
  • Laura E. Phelps, Jacob D. Peuler
    Type: Original
    Volume 46 (2010) Issue 3 Pages 125-142
    Released: July 15, 2010
    JOURNALS FREE ACCESS
    Fibrates are commonly employed to treat abnormal lipid metabolism via their unique ability to stimulate peroxisome proliferator-activated receptor alpha (PPARα). Interestingly, they also decrease systemic arterial pressure, despite recent evidence that PPAR α may contribute to expression of renin and related hypertension. Yet, mechanisms responsible for their potential antihypertensive activity remain unresolved. Rapid decreases in arterial pressure following bolus intravenous injections of bezafibrate strongly suggest they may relax arterial smooth muscle directly. But since bezafibrate is highly susceptible to photodegradation in aqueous media, it has never been critically tested for this possibility in vitro with isolated arterial smooth muscle preparations. Accordingly, we tested gemfibrozil which is resistant to photodegradation. We examined it over a therapeutically-relevant range (50–400 μM) for both acute and delayed relaxant effects on contractions of the isolated rat tail artery; contractions induced by either depolarizing its smooth muscle cell membranes with high potassium or stimulating its membrane-bound receptors with norepinephrine and arginine-vasopressin. We also examined these same gemfibrozil levels for effects on spontaneously-occurring phasic rhythmic contractile activity, typically not seen in arteries under in vitro conditions but commonly exhibited by smooth muscle of uterus, duodenum and bladder. We found that gemfibrozil significantly relaxed all induced forms of contraction in the rat tail artery, acutely at the higher test levels and after a delay of a few hours at the lower test levels. The highest test level of gemfibrozil (400 μM) also completely abolished spontaneously-occurring contractile activity of the isolated uterus and duodenum and markedly suppressed it in the bladder. This is the first evidence that a fibrate drug can directly relax smooth muscle contractions, either induced by various contractile agents or spontaneously-occurring. These findings are particularly relevant to both the recently renewed concern over the impact of fibrates on hypertension and a new understanding of their gastrointestinal side effects.
    View full abstract
    Download PDF (318K)
  • Hiroko Matsuyoshi, Tadashi Nakagawa, Guo-Xing Zhang, Koji Obata, Hirom ...
    Type: Original
    Volume 46 (2010) Issue 3 Pages 143-156
    Released: July 15, 2010
    JOURNALS FREE ACCESS
    Purpose: In the ileum of W/Wv mutant mice (W/Wv), the absence of interstitial cells of Cajal (ICC) in the myenteric region (ICC-MY), and cross-talk between ICC in the deep muscular region (ICC-DMP) and enteric nitrergic motor nerves leads to irregular spontaneous electrical and contractile activity. The aim of the present study was to reveal changes in this irregular spontaneous electrical and contractile activity in the ileum of dextran sodium sulfate (DSS: m.w. 40,000)-induced colitis model W/Wv mice. Methods: Electrical and contractile activity was recorded with a suction electrode and with both an isometric force transducer and a pressure transducer in the ileum of W/Wv mice either with DSS-induced colitis (DSS (+)) in the distal colon or without in controls (DSS (–)). Neuronal NO synthase (nNOS) and inducible NO synthase (iNOS) immunoreactivity in the ileum was compared between the following groups of mice: W/Wv DSS (+), W/Wv DSS (–), wild type (WT) with (DSS (+)) and WT without DSS-induced colitis (DSS (–)). Results: DSS induced colitis in the distal colon of W/Wv mice is reduced compared with that in WT mice, despite the reduction in the number of mast cells in the W/Wv mutants. Irregular contractions in the ileum without colitis were strongly suppressed in W/Wv DSS (+) mice. The mean interval of irregular contractions in W/Wv DSS (+) mice was 5-fold larger than that in W/Wv DSS (–) mice. N-nitro-L-arginine methyl ester (L-NAME) facilitated the frequency of irregular contractions in the ileum without colitis in W/Wv DSS (+) mice. L-NAME decreased the mean interval of contractions to one-fourth in the ileum of W/Wv DSS (+) mice, where strong iNOS immunoreactivity in nitrergic motor nerves was found with unchanged nNOS immunoreactivity. Conclusions: The stronger suppression of irregular contractions of the ileum in DSS-induced colitis model W/Wv mice was elicited and mediated by cross-talk between ICC-DMP and enteric nitrergic motor nerves expressing iNOS/NO, even though the ileum was not demonstrating colitis.
    View full abstract
    Download PDF (404K)
  • Fedoua Gandia, Sonia Rouatbi, Imed Latiri, Hervé Guénard ...
    Type: Original
    Volume 46 (2010) Issue 3 Pages 157-164
    Released: July 15, 2010
    JOURNALS FREE ACCESS
    Asthma is a global health problem. Asthma attacks are becoming more severe and more resistant to usual treatment by β2 agonists nebulisation. The search for a new product that could reduce the morbidity of asthmatic disease seems necessary. The objective of this study was to compare the effectiveness of inhaled magnesium fluoride (MgF2) with that of magnesium sulphate (MgSO4) 15% alone and sodium fluoride (NaF) 0.5 M alone in rats pre-contracted by methacholine (MeCh). Fifty six adult male Wistar rats of medium weight 259 ± 15 g were divided randomly into five groups. They inhaled respectively: MeCh, MgF2 + NaCl 0.9%, MgF2 + acetic acid, MgSO4 15% single and NaF (0.5 M) single. Airway resistances were measured after each dose of MeCh by pneumomultitest equipment. Results indicated that (1) MgF2 + NaCl 0.9%, MgF2 + acetic acid and MgSO4 reversed significantly the methacholine-induced bronchial constriction in rats and had a bronchodilating effect at the moment of its administration (2) MgF2 + acetic acid led to a greater decrease (P<0.05) of bronchial resistances when compared to that obtained from MgF2 + NaCl 0.9%, NaF exclusively and MgSO4 alone (3) inhaled NaF alone led to a significant bronchorelaxing effect (P<0.05) that starts at the sixth dose of MeCh (17 mg/L). As a matter of fact, MgF2 dissolved in acetic acid and delivered in aerosol form reduces significantly bronchial spasm. In conclusion, MgF2 can be used as a bronchodilator for diseases with bronchospasma such as asthma and chronic obstructive pulmonary disease (COPD).
    View full abstract
    Download PDF (123K)
  • Mounia Skiker, Hassane Mekhfi, Mohamed Aziz, Benyounes Haloui, Saad La ...
    Type: Original
    Volume 46 (2010) Issue 3 Pages 165-174
    Released: July 15, 2010
    JOURNALS FREE ACCESS
    Artemisia herba-alba Asso (Compositae) is used in oriental Morocco to treat diabetes and arterial hypertension. The present work evaluated the vasorelaxant effect of Artemisia herba-alba aqueous extract (AHAE) in isolated rat aorta and the mechanism underlying this effect. In endothelium-containing aorta preparations, AHAE (10–3, 10–2, 10–1, 1 and 2 mg/mL) relaxed the contraction elicited by noradrenaline in a concentration-dependent manner. This effect is dependent upon integrity of the vascular endothelium as it was fully abolished in endothelium-denuded preparations. The vasorelaxant effect of AHAE (2 mg/mL) was also inhibited by NG-nitro-L-arginine methyl-ester (100 μM), methylene blue (10 μM) or 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (50 μM) but not by 10 μM atropine. This effect remained unchanged by tetraethylammonium (5 mM) or indomethacin (10 μM) whereas it was significantly attenuated by glibenclamide (10 μM). These results suggest that AHAE produces an endothelium-dependent relaxation of the isolated rat aorta, an effect that seems mainly mediated through stimulation of the endothelial nitric oxide synthase by mechanisms other than activation of muscarinic receptors. Activation of ATP-dependent potassium channels partly contributes in the mediation of AHAE-induced endothelium-dependent relaxation.
    View full abstract
    Download PDF (266K)
    • |<
    • <
    • 1
    • >
    • >|
feedback
Top