Human postmortem digital arteries obtained between 6 and 60 hours after death were used for in vitro studies of vascular smooth muscle physiology and pharmacology. Isometric tension was recorded from spiral strips in tissue baths at 37°C. The responses were durable and reproducible and were similar to those of 10 operative specimens of visceral arteries. The contractile force of the preparations was unrelated to the time elapsed since death. Norepinephrine, 5-hydroxytryptamine, and barium chloride gave the strongest responses; histamlne and potassium chloride were weaker agonists. Hie order of sensitivities to the agonists tested was angiotensin > 5hydroxytryptamine > norepinephrine > histamlne > barium chloride > potassium chloride. Both competitive (phentolamlne) and noncompetitive (phenoxybenzamlne) antagonism of DorepiDephrine was demonstrated. Pbentolamine was also a weak inhibitor of 5-hydroxytryptamine. Cyprobeptadine was a potent antagonist of 5-hydroxytryptamine, but had less effect against norepinephrine. This suggests the presence of separate receptors for 5hydroxytryptamine and norepinephrine in these vessels. The response to barium chloride was inhibited by the calcium-antagonist, verapamil. The o-adrenoceptor antagonist, phentolamlne, was not effective against barium chloride. We conclude that human postmortem digital arteries can be studied effectively in vitro. The preparation should be useful for the evaluation of drugs that are thought to act at a peripberal vascular site.
1. Spiral strips of human digital arteries have been studied in vitro to investigate whether DL-propranolol, D-propranolol, oxprenolol and labetalol have peripheral vascular effects in man. 2. Labetalol was a potent inhibitor of contractile responses to noradrenaline, but had less effect on responses to 5-hydroxytryptamine and barium chloride. 3. DL-and D-propranolol were equally effective inhibitors of responses to barium chloride. They were only weak antagonists of noradrenaline responses, but stronger, non-competitive antagonists of 5-hydroxytryptamine responses. 4. Oxprenolol was only a weak inhibitor of the responses to both noradrenaline and 5-hydroxytryptamine and had little effect on responses to barium chloride. 5. It is concluded that labetalol has specific alpha-adrenoreceptor-blocking properties, which are probably relevant to its therapeutic action in man. Propranolol has non-specific inhibitory effect on vascular smooth muscle, which might contribute to its hypotensive activity at high concentrations, but oxprenolol has only slight peripheral effects that are probably therapeutically insignificant.
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