The Characteristics of Contractions to Hyperosmolar Stress in Rat Aorta

Buharalioglu C. K., UĞUR M., AKAR F.

INTERNATIONAL JOURNAL OF PHARMACOLOGY, vol.7, no.3, pp.340-348, 2011 (SCI-Expanded) identifier identifier


The aim of this study was to determine the characteristics of hyperosmolarity-induced contractions using inhibitors of the effectors for contractile process that are activated by hyperosmolarity, such as Na(+)-K(+)-2Cl(-) cotransporter (NKCCl) and Myosin Light Chain Kinase (MLCK). Hyperosmolar sucrose (80, 160, 320 and 640 mM) or NaCl (40, 80, 160 and 320 mM) solutions were applied to isolated aortic rings of rats. Inhibitors of contractile process; namely, bumetanide (NKCCl), nifedipine (L-type calcium channel), thapsigargin (sarcoplasmic reticulum Ca(2+)-ATPase), wortmannin (MLCK), 2,3-butanedione monoxime (BDM; myosin ATPase) were tested on sucrose (320 mM) and NaCl (160 mM)-induced contractions. Intracellular calcium ([Ca(2+)](i)) measurements, based on F(340/380), were performed on fura2-AM loaded aorta. Increasing the osmolarity with sucrose or NaCl caused slow developing and sustained contractions in rat aortic rings. Nifedipine (10(-6) M) or removal of extracellular Ca(2+) slightly reduced hyperosmolar NaCl or sucrose-induced contractions. Thapsigargin (10(-6) M) increased sucrose but did not change NaCl-induced contractions. [Ca(2+)](i), did not change following exposure to hyperosmolar solutions. Bumetanide (10(-7)-10(-4) M) and wortmannin (10(-7)-4x10(-6) M) moderately inhibited hyperosmolarity-induced contractions. However, BDM (0.1-20 mM) caused a concentration-dependent and profound inhibition on these contractions. Moreover, BDM (10 mM) produced marked relaxations in arterial rings precontracted with hyperosmolar NaCl or sucrose. NaCl-induced contraction was more resistant to the inhibitors, indicating sucrose and NaCl have different contractile characteristics. Hyperosmolarity-induced contractions are explained partially by activation of NKCCl and MLCK. BDM-sensitive mechanisms have a primary importance in these contractions.