Contraction induced by hyposmotic swelling was examined in rat tail arteries mounted on a myograph containing a modified Krebs physiological saline solution (PSS) containing 50 mM mannitol (300 mosm/l). Hyposmotic swelling was induced by removing mannitol. In arteries having basal tone or arteries precontracted with K+ or the thromboxane mimetic U-46619, removal of mannitol caused a concentration dependent contraction of rat tail arteries. Concurrent measurement of tension and intracellular calcium [Ca2+]i in arteries loaded with fura-2 showed that both tension and [Ca2+]i increased on exposure to a hyposmotic solution. Removal of endothelium or inhibition of nitric oxide and cyclooxygenase together did not affect contractile responses. Removal of extracellular Ca2+ abolished the contractile response to hyposmotic solution and NiCl2, a nonspecific inhibitor of Ca2+ influx pathways, blocked the rise in [Ca2+]i and tension in response to a hyposmotic solution. Verapamil and nisoldipine, inhibitors of Cav1.2 (L-type) calcium channels significantly reduced the contractile response to a hyposmotic solution. Addition of NiCl2 to nisoldipine caused an additional inhibition of the response to a hyposmotic solution. Inhibition of calcium release from the sarcoplasmic reticulum by ryanodine or cyclopiazonic acid (CPA) did not cause any change in the tension response to a hyposmotic solution. CPA did not significantly inhibit the response to a hyposmotic solution in the presence of NG-methyl-L-arginine, oxyhaemoglobin and indomethacin. We conclude that contraction induced by a hyposmotic solution is largely due to Cav1.2 calcium channels although other Ca2+ influx pathways also contribute.

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