Differences in sensitivity to vasoconstrictor drugs within the wall of the sheep carotid artery.

1. Controlled heat damage was used to separate the responses of the outer innervated smooth muscle from those of the inner nerve-free smooth muscle of the sheep carotid artery.2. Preparations of smooth muscle from the inner part of the media gave 50% maximal contractions in response to approximately 1/15 the concentration of noradrenaline needed to produce similar responses from outer smooth muscle. The difference in sensitivity was greater in the lower than the upper parts of the dose-response curves.3. Much of the difference in sensitivity was still seen in the presence of Desipramine and after chronic denervation, and so could not be attributed to uptake of noradrenaline by the nerve fibres in the outer smooth muscle; disappearance of the fibres after denervation was confirmed by fluorescence microscopy.4. Similar but generally smaller differences in sensitivity between inner and outer smooth muscle were seen with respect to histamine, angiotensin II and 5-hydroxytryptamine.5. Sympathetic denervation 10-14 days previously increased the sensitivity of outer strips to noradrenaline; it usually also increased their sensitivity to histamine, suggesting that the change largely represented non-specific denervation super-sensitivity.6. The high sensitivity of the inner smooth muscle is likely to be of value in enabling it to respond to the relatively low concentration of noradrenaline reaching it in life.