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Infusions of bretylium and guanethidine into the brachial artery of normal subjects caused a fall in forearm and hand blood flow followed by a sustained increase in flow. The constrictor phase was attributed to catechol amine release since it was blocked by phenoxybenzamine. A slight and transient increase in response of the hand vessels to noradrenaline was seen after bretylium in the early constrictor phase before sympathetic block was complete. Guanethidine produced a more definite and sustained increase in the response of the hand vessels to noradrenaline. It is concluded that the phenomenon of tolerance which is conspicuous with bretylium and negligible with guanethidine is unlikely to be due to the rapid onset of hypersensitivity of the peripheral vessels.

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