An investigation of the actions of diltiazem on rat aorta exposed to acute hypoxia followed by re-oxygenation.
1 The effects of diltiazem and removal of extracellular Ca2+ were examined on contractions, of the rat isolated aorta, to noradrenaline (NA) and high K+, during exposure to oxygenated conditions and hypoxia followed by re-oxygenation. 2 Exposure to hypoxia caused a similar reduction of contractile responses to NA and KCl, while re-oxygenation restored contractile activity. 3 Ca2+-free conditions abolished responses to KCl but a transient response to NA remained which was resistant to hypoxia. 4 Diltiazem produced similar reductions of responses to NA during both oxygenated conditions and hypoxia, whereas during re-oxygenation the effects of diltiazem upon responses to NA were enhanced. 5 Diltiazem produced a more pronounced reduction of responses to KCl than of responses to NA. However, the reduction of responses to KCl by diltiazem was not modified by the changes in PO2 examined in the present study. 6 The present study indicates that contractions of the rat aorta mediated by intracellular Ca2+ are resistant to the hypoxic conditions studied in the present investigation, whereas those responses mediated by an influx of Ca2+ are reduced. The increase in the contractile response to NA following re-oxygenation may result from an increased influx of extracellular Ca2+ since such responses show an enhanced sensitivity to diltiazem.
Marriott
J F
JF
Department of Pharmaceutical Sciences, Aston University, Birmingham.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010100:Oxygen / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D004110:Diltiazem; D010100:Oxygen; D002118:Calcium