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  • Title: Characteristics of depression by clonidine of the pressor response to alpha 1-adrenoceptor agonists in pithed rats.
    Author: Nomura S, Sunagane N, Uruno T, Kubota K.
    Journal: Res Commun Mol Pathol Pharmacol; 1996 Mar; 91(3):273-86. PubMed ID: 8829767.
    Abstract:
    Effects of clonidine on the elevated arterial diastolic blood pressure induced by infusion of alpha 1-adrenoceptor agonists were studied in pithed rats. Intravenous injection of clonidine resulted in a dose-dependent pressor response at a resting state and a further increase in the moderately elevated diastolic blood pressure induced by infusion of lower doses of phenylephrine and methoxamine. However, clonidine produced a depressor response when diastolic blood pressure was elevated by around 100 mmHg during infusion of higher doses of alpha 1-adrenoceptor agonists. The depressor response to clonidine was dose-dependent at a dose range of 10 to 1000 micrograms/kg. On the other hand, clonidine failed to cause the depressor response while diastolic pressure was elevated by infusion of vasopressin by around 100 mmHg. NG-methyl-L-arginine, a nitric oxide synthase inhibitor, and propranolol, a beta-adrenoceptor antagonist, did not affect the depressor response to clonidine. After pretreatment with yohimbine, an alpha 2-adrenoceptor antagonist, the depressor response to clonidine was inhibited, but prazosin, an alpha 1-adrenoceptor antagonist, did not suppress the depressor response. These results demonstrate that clonidine specifically depresses the pressor response to alpha 1-adrenoceptor agonists in pithed rats via a mechanism which is not mediated by beta-adrenoceptors and independent of endothelium-dependent relaxing factor, and suggest that a yohimbine-sensitive mechanism may be related to the clonidine effect.
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