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Cardiovascular response to beta-hydroxy thujaplicin and gamma-thujaplicin.

University of British Columbia

An Investigation was undertaken to determine the effects of beta-hydroxy thujaplicin and gamma-thujaplicin, used as the sodium salts, on blood pressure and heart rate in the rat. Attempts were made to discover the sites and modes of action of these two compounds. Gamma-thujaplicin 30mg/kg. produced either a vasopressor or a vasodepressor response in anesthetized rats. The pressor response was usually more pronounced, than the vasodepressor response. Tachycardia occurred with either blood pressure response. To determine whether the central nervous system was necessary for the vasopressor and tachycardiac response, pithed rats were used. In these preparations gamma-thujaplicin produced only a fall in blood pressure and a decrease in heart rate. The effect of adrenergic blocking drugs on the response to gamma-thujaplicin was investigated. In the anesthetized rat the vasopressor response was reduced significantly by both phenoxybenzamine and pronethalol; however, the heart rate was unaffected. In the pithed rat the vasodepressor response produced by gamma-thujaplicin was not affected by pronethalol; however, gamma-thujaplicin produced a significantly greater decrease in heart rate after treatment with pronethalol. To determine whether gamma-thujaplicin had adrenergic alpha-receptor or beta-receptor blocking properties its effect on blood pressure responses to noradrenaline and isoproterenol was investigated. Gamma-thujaplicin was found to reduce the vasopressor effect of intravenous noradrenaline 0.5ug/kg. but had no effect on the vasopressor response produced by isoproterenol 0.25ug/kg. The pressor response to intravenous physostigmine salicylate 40ug/kg. was unaffected by gamma-thujaplicin. The increase in heart rate and blood pressure produced by gamma-thujaplicin, with injections repeated every fifteen minutes, was greatly reduced after the second dose. It is concluded that in the anesthetized rats the vasopressor and tachycardiac response produced by gamma-thujaplicin were of central origin while the vasodepressor effect was a result of direct action on vascular smooth muscle. The vasopressor response could involve the stimulation, via sympathetic nerves, of alpha-adrenergic receptors of vascular smooth muscle. Gamma-thujaplicin can produce alpha-adrenergic receptor, blockade to exogenous noradrenaline, but not to endogenously released noradrenaline since the response to intravenous physostigmine was not affected by the tropolone. Beta-hydroxy thujaplicin 10mg/kg. caused a vasopressor response in all anesthetized and pithed rats tested. The vasopressor response was abolished by phenoxybenzamine in both anesthetized and pithed rats. Beta-hydroxy thujaplicin did not alter isoproterenol induced tachycardia or the vasopressor response produced by physostigmine salicylate. It is concluded that beta-hydroxy thujaplicin caused its vasopressor effect in rats by acting directly on the alpha-adrenergic receptors of vascular smooth muscle.

Text

2011-05-19

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http://hdl.handle.net/2429/34714

Pharmacology

University of British Columbia

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