Involvement of α₁- and α₂-adrenoceptors in the responses of proximal and distal segments of the canine saphenous vein to exogenous and endogenous noradrenaline

Summary

In the present study the relationship between adrenergic nerve terminals and postjunctional α-adrenoceptors mediating the responses to the endogenous transmitter was compared at proximal and distal levels of the canine saphenous vein.

Concentration-response curves to noradrenaline and to tyramine as well as frequency-response curves to electrical stimulation were compared at both levels of the vessel, in the absence and presence of either prazosin (100nmol·l⁻¹) or yohimbine (100nmol·l⁻¹) The influence of inhibition of neuronal uptake by cocaine (12 µmol·l⁻¹) on the responses to noradrenaline in the presence of prazosin (56 nmol·l⁻¹) or yohimbine (20 nmol·l⁻¹) was compared at the proximal level. The results show that, at the proximal level, the maximal responses to electrical stimulation and tyramine reached 80.1±2.2 (n = 18) and 74.2±1.9 (n = 18)%, respectively, of the maximal responses to noradrenaline, and 70.3±0.8 (n = 15) and 53.1 ± 1.2 (n = 14) %, respectively, at the distal level. Furthermore, the proximal strips were more sensitive to electrical stimulation than the distal ones. Prazosin had a much greater inhibitory effect on the contractile responses to noradrenaline than on those to electrical stimulation, at both levels. At proximal level, the shifts (to the right) of the concentration (frequency)-response curves (at EC₅₀) amounted to 0.58±0.02 (n = 16) and 0.18±0.02 (n = 8) log units, respectively (P<0.05), but, at the distal level, to 1.12±0.03 (n = 16) and 0.28±0.08 (n = 8) log units, respectively (P< 0.05). At the proximal level, yohimbine antagonizes about equally the responses to noradrenaline and the responses to electrical stimulation. However, at the distal level, the shift of the concentration-response curve to noradrenaline was much larger than that of the frequency-response curve to electrical stimulation [1.12±0.07 and 0.80±0.10 (n = 6) log units at EC₅₀, respectively (P<0.05)]. The leftward shift of the concentration-response curve to noradrenaline caused by cocaine was more pronounced in the presence of prazosin than in the presence of yohimbine: 0.95±0.15 and 0.69±0.12 (n = 12) log units, respectively (P<0.05).

We conclude that, in the canine saphenous vein: 1) noradrenaline released from the adrenergic nerve terminals by electrical stimulation and by tyramine preferentially activates α₂-adrenoceptors at both proximal and distal levels; 2) the effectiveness of α₂-adrenoceptor stimulation is greater at the proximal than at the distal level; 3) α₁-adrenoceptors at the distal level seem to be different from those at the proximal one.