Neurotransmission in Human Resistance Arteries: Contribution of Alpha 1- and Alpha 2-adrenoceptors but Not P 2-purinoceptors

The contribution of postjunctional alpha 1- and alpha 2-adrenoceptors and P2-purinoceptors to the neuroeffector response was examined in isolated segments of human subcutaneous resistance arteries. Electrical field stimulation (EFS, 20 V, 0.2 ms, 1-25 Hz) elicited a maximum contractile response which was 38.2 +/- 1.6% of that elicited by exogenously applied (5 microM) noradrenaline (n = 56). Tetrodotoxin (1 microM), used to inhibit neurotransmission, reduced the electrically evoked response to 24.7 +/- 4.4% (n = 10) of the control response. The alpha 1-adrenoceptor antagonist prazosin (1 microM) reduced the maximum EFS contractile response to 64.8 +/- 5.5% of the control response (n = 17). Application of the alpha 2-adrenoceptor antagonist yohimbine (0.1 microM) reduced the maximum EFS response to 68.2 +/- 8.2% of the control response (n = 9). In the presence of prazosin plus yohimbine at the above-mentioned concentrations the maximum response to EFS was reduced to 47.6 +/- 6.7% (n = 11). Responses following alpha-blockade were not statistically different from those in the presence of tetrodotoxin, but the mean responses indicate that a non-adrenergic component to the EFS response cannot be discounted. Desensitisation of P 2-purinoceptors with alpha, beta-methylene ATP had no effect on responses to EFS; therefore under the conditions studied these receptors do not appear to be involved in neurotransmission. These results confirm the presence of postjunctional alpha 1- and alpha 2-adrenoceptors in human resistance arteries and for the first time demonstrate that the postjunctional alpha 2-adrenoceptor is important in modulating vascular responses elicited by intramural sympathetic nerve fibres.