The influence of various alpha-adrenoceptor antagonists (phentolamine, yohimbine, R 28935, prazosine, terazosine) on clonidine's blood pressure effects at different steady state plasma concentrations was investigated in awake spontaneous hypertensive rats. Clonidine's threshold (greater than 10 mmHg, less than 20 mmHg) antihypertensive effect was potentiated by phentolamine but opposed by centrally acting antagonists as was the maximal antihypertensive effect. The pressor response on the other hand was blocked by peripherally acting alpha-1- and alpha 2-antagonists. The effect of clonidine on blood pressure thus seems a consequence of both the tissue distribution and the alpha-adrenoceptor affinity. At low steady state plasma concentrations of clonidine a peripheral action could be a part of the antihypertensive mechanism.
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Marianne Frisk‐Holmberg (1984) studied this question.
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