Mechanism of contraction of rat isolated tail arteries by hyposmotic solutions.
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 [Ca(2+)](i )in arteries loaded with fura-2 showed that both tension and [Ca(2+)](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 Ca(2+) abolished the contractile response to hyposmotic solution and NiCl(2), a nonspecific inhibitor of Ca(2+) influx pathways, blocked the rise in [Ca(2+)](i) and tension in response to a hyposmotic solution. Verapamil and nisoldipine, inhibitors of Ca(v)1.2 (L-type) calcium channels significantly reduced the contractile response to a hyposmotic solution. Addition of NiCl(2) 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 N(G)-methyl-L-arginine, oxyhaemoglobin and indomethacin. We conclude that contraction induced by a hyposmotic solution is largely due to Ca(v)1.2 calcium channels although other Ca(2+) influx pathways also contribute.
Wijetunge
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Clinical Pharmacology, NHLI Division, Faculty of Medicine, Imperial College London, South Wharf Road, London W2 1NY, UK.
Hughes
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D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D007552:Isotonic Solutions / Q000494:pharmacology*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000502:physiology; D009994:Osmolar Concentration; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013623:Tail / Q000098:blood supply*; D014661:Vasoconstriction; D014666:Vasomotor System / Q000187:drug effects
D020746:Calcium Channels, L-Type; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; C419385:L-type calcium channel alpha(1C); D008353:Mannitol; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D002118:Calcium