The Pharmacology of Calcium Antagonists on Normal and Hypoxic Vascular Muscle

  • John F. Marriott

Student thesis: Doctoral ThesisDoctor of Philosophy


The effects of calcium entry blockade and nitroprusside were examined upon responses of ring preparations of the rat aorta to NA or KC) during normoxia (pO2»3?4maHg) and acute (30min) or chronic (70 hours) hypoxia with re-oxygenation. These agents were also compared using isolated rat portal veins and perfused aesenteric beds.

Calcium entry blockade was ineffective against responses of the rat aorta
mediated by intracellular Ca?*, yet reduced those mediated by extracellular Ca2+ with a preferential action against those induced by KCl. Nitroprusside produced a
preferential reduction of responses of the rat aorta mediated by intracellular Ca2+.

Exposure to acute or chronic hypoxia caused similar reductions of the responses
of the rat aorta to NA or KCL, which recovered upon re-oxygenation (the recovery response). Responses mediated by intracellular Ca2+ appeared to be resistant to hypoxia. Exposure to acute hypoxia did not change the sensitivity to calcium entry blockade of responses to NA, whereas nitroprusside became more effective. The calcium entry blockers were more effective against recovery responses to NA, yet the sensitivity of these responses to nitroprusside decreased. No corresponding changes in the sensitivity of responses to KC1 were observed.

Responses of the rat aorta to NA were refractory and those to KC1 were aore
resistant to calcium entry blockade following chronic hypoxia. There was no change in the sensitivity to nitroprusside of responses following chronic hypoxia.

In the rat aorta, hypoxia aight cause a reduction in Ca?* entry through a pathway
sensitive to calcium entry blockade, whereas, recovery responses appear to be mediated by Ca2+ which enters through a pathway which is sensitive to calcium entry blockade. Variations in the selectivity of calcium entry blockers and nitroprusside and the effects of hypoxia are reported between different vessels.
Date of Award1985
Original languageEnglish


  • pharmacology
  • calcium antagonists
  • normal
  • hypoxic
  • vascular muscle

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