title: Mechanism of acidic pH-induced contraction in spontaneously hypertensive rat aorta: role of Ca2+ release from the sarcoplasmic reticulum.
abstract: OBJECTIVE
  This study was conducted to investigate the mechanism of acidic pH-induced contraction (APIC) with regard to Ca2+ handling using isometric tension recording experiments.
  
  
  RESULTS
  Decreasing extracellular pH from 7.4 to 6.5 produced a marked and sustained contraction of spontaneously hypertensive rat (SHR) aorta, that was 128.7 +/- 2.0% of the 64.8 mm KCl-induced contraction. Verapamil, an inhibitor of voltage-dependent Ca2+ channels (VDCC) significantly inhibited the APIC. In Ca2+-deficient solution, sustained contraction induced by acidic pH was abolished completely, while a transient contraction was still observed suggesting the release of Ca2+ from intracellular site. Ryanodine (1 microm), a ryanodine receptor blocker, and 10 microm cyclopiazonic acid (CPA; a sarco/endoplasmic reticulum Ca2+ ATPase inhibitor) abolished the transient contraction induced by acidosis. In normal Ca2+-containing solution, ryanodine significantly decreased the rate of rise as well as maximum level of APIC. Interestingly, ryanodine and CPA showed an additive inhibitory effect with verapamil and the combined treatment of ryanodine or CPA with verapamil nearly abolished the APIC.
  
  
  CONCLUSIONS
  It is concluded that acidic pH induces Ca2+ release from ryanodine/CPA-sensitive store of sarcoplasmic reticulum in SHR aorta. This Ca2+ plays an important role in the facilitation of the rate of rise of APIC, as well as contributing to the sustained contraction via a mechanism which is independent of Ca2+ influx through VDCC.
authors: Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai, Japan.
authors: D K
authors: DK
authors: Rohra
authors: S-Y
authors: SY
authors: Saito
authors: Y
authors: Y
authors: Ohizumi
mesh_terms: D000138:Acidosis / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D012433:Ryanodine; D004533:Egtazic Acid; D014700:Verapamil; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid