Neurally evoked responses of human isolated resistance arteries are mediated by both αm1‐ and α2‐adrenoceptors

Abstract

Human subcutaneous resistance arteries (internal diameter 113–626 μm) were mounted in an isometric myograph. Electrical field stimulation was applied either continuously in the form of a frequency‐response curve or intermittently at 16 Hz. The magnitude of the maximum contraction induced by continuous stimulation expressed as a percentage of the response to a supramaximal concentration of noradrenaline (10 μm) was highly variable but unrelated to vessel calibre. Contractile responses to both continuous and intermittent stimulation were abolished by 1 μm tetrodotoxin. Prazosin (100 nm and 1 μm, α1‐adrenoceptor antagonist) inhibited responses to continuous stimulation over a range of frequencies (2–8 Hz). The response to continuous stimulation at 8 Hz was inhibited by 78 ± 6% by 1 μm prazosin. Rauwolscine (100 nm, α2‐adrenoceptor antagonist) had a smaller effect on contractions induced by continuous stimulation. Rauwolscine inhibited the response at 8 Hz by 36 ± 6%. Rauwolscine at a higher concentration (1 μm) caused further inhibition of the response to continuous stimulation. Prazosin and rauwolscine in combination almost completely inhibited the response to continuous stimulation at concentrations of 1 μm. Prazosin and rauwolscine inhibited responses to intermittent stimulation in a concentration‐dependent manner. The IC50 for this action of prazosin was 3.7 ± 1.6 nm and the maximum inhibition induced by 100 nm prazosin was 78 ± 6%. The IC50 of rauwolscine was 12.0 ± 1.3 nm and 100 nm rauwolscine caused a 86 ± 7% reduction in the response to intermittent stimulation. Prazosin and rauwolscine in combination (each at 100 nm) caused marked inhibition of the response to intermittent stimulation leaving only 7.0 ± 2.6% of the response. These data suggest that neurally released noradrenaline evokes contractions of human resistance arteries by activation of both α1 and α2‐adrenoceptors postjunctionally. 1992 British Pharmacological Society