Browsing by Subject "1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine"

Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    Contribution of RhoA kinase and protein kinase C to weak relaxant effect of pinacidil on carbachol-induced contractions in sensitized guinea-pig trachealis
    (2009) Gok S.; Izanli-Paksoy A.; Vural K.
    The exact mechanisms underlying the weak bronchodilator effect of K ATP channel openers on cholinergic stimulations is unknown. The present study was designed to examine the relaxant efect of pinacidil in guinea-pig trachea stimulated with carbachol by the presence of calcium sensitizer inhibitors; HA 1077, a rhoA kinase inhibitor, and chelerythrine, a protein kinase C inhibitor. Adenosine (10 μM) was used as other contractile agent for comparison. Tracheal tissues were isolated from ovalbumin sensitized guineapigs and changes in tension were recorded isometrically. Pinacidil (1-100 μM, cumulatively) and HA 1077 (0.01-30 μM, cumulatively) produced concentration-dependent relaxations in unstimulated tisues. The relaxant response to pinacidil decreased in carbachol contracted tissues, but increased in adenosine-stimulated tissues. Pretreatment of the tissues with HA 1077 (0.1 μM) and chelerythrine (10 μM) increased the pinacidil-induced relaxations by ∼%100 and %40, respectively. Glibenclamide, a KATP channel blocker, partially antagonized the pinacidil response in contracted tissues. Glibenclamide also inhibited the carbachol and adenosine induced contractions. These results suggest that diminish effect of pinacidil may have related to the enhanced calcium sensitization by cholinergic stimulation. Rho kinase inhibitors appear more effective than PKC inhibitors to achieve of this failure. © 2009 The Pharmaceutical Society of Korea.
  • No Thumbnail Available
    Item
    Vasodilator effects of cromakalim and HA 1077 in diabetic rat aorta
    (SMW supporting association, 2012) Gurpinar T.; Gok S.
    BACKGROUND: Impairment of the vasorelaxant responses have been reported in diabetes mellitus. In this study, the roles of the KATP channel and rho kinase pathway were evaluated by using the KATP channel opener cromakalim and Rho-kinase inhibitor HA 1077 in diabetic rat aorta. METHODS: Adult male Wistar rats weighing (250-300 g) were divided into diabetic and control groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 55 mg/kg/i.p). RESULTS: Vasodilator responses induced by cromakalim (10-7 to 10-3M) and HA 1077 (10-6 to 10-4M) were significantly less in diabetic rings compared with control rings (p <0.01). The decrease in the relaxant effect of cromakalim was more in endothelium-denuded rings compared to the endothelium-intact rings (p <0.05). There were no significant differences between endothelium intact and nonintact rings in the presence of HA 1077. When two drugs were administered together, relaxation was significantly less than with seperate administration of each drug in the diabetic group (p <0.01). Pre-treatment with N omeganitro- L-arginine methylester (L-NAME) (10-6 to 10-4 M), an NO synthase inhibitor, significantly decreased the relaxant response to cromakalime and HA 1077 in both the control and diabetic groups (p <0.05). CONCLUSIONS: These results suggest that the impaired relaxant effects were further decreased depending on KATPchannel activity but the effects of Rho-kinase enzyme inhibitors on relaxation responses were not significantly changed in diabetes mellitus.