A quantitative analysis of the antagonism of intravenous noradrenaline by thymoxamine or phentolamine on the blood pressure of the conscious cat

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Abstract
The blood pressure of the unanaesthetized cat was recorded from a nylon catheter inserted permanently into the aorta via the right carotid artery and intravenous injections were made into a nylon catheter tied permanently into the right external jugular vein. For noradrenaline there was a linear relation between log dose and blood pressure rise. The α-blocking agents thymoxamine and phentolamine lowered the blood pressure and decreased the pressor response to noradrenaline. Quantitative analysis of the results by three different graphical methods revealed that for the first dose of blocking agent the antagonism was complex but had the characteristics associated with mixed non-competitive and uncompetitive antagonism. For further cumulative doses of blocking agent, the antagonism had the characteristics of competitive antagonism. It is concluded that a first dose of α-blocking agent has an effect on the dynamics of a noradrenaline-induced blood pressure rise in the conscious cat which is complex and could in part be due to the initial effect of the blocking agent in lowering the blood pressure and in part to the activity of the vasomotor compensatory reflexes. After α-blockade has been initiated, the characteristics of the antagonism are, like those in the anaesthetized cat, those of competitive antagonism.

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