Pharmacological characterization of noradrenaline‐induced contractions of the porcine isolated palmar lateral vein and palmar common digital artery

1 The aim of this study was to examine the pharmacological characteristics of α‐adrenoceptor‐mediated contractions in two porcine isolated blood vessels, the palmar lateral vein (PLV) and the palmar common digital artery (PCDA). This was carried out with noradrenaline used as the agonist throughout, and either phentolamine (non‐selective α‐adrenoceptor antagonist), prazosin and YM‐12617 (selective α 1 ‐adrenoceptor antagonists) or rauwolscine and CH‐38083 (selective α 2 ‐adrenoceptor antagonists). 2 Noradrenaline (0.003–10 μ m ) produced concentration‐dependent contractions in both vessels, with the PCDA (pD 2 = 6.33 ± 0.07, n = 10) being approximately 10 fold less sensitive to noradrenaline compared to the PLV (pD 2 = 7.39 ± 0.09, n = 8). Also, the maximal response to noradrenaline was greater in the PCDA compared to the PLV. Phentolamine (0.03–30 μ m ) produced parallel rightward shifts in the CRC to noradrenaline in both tissue preparations. The pA 2 values were similar and slopes of the Schild plots were not significantly different from unity, indicating an interaction between phentolamine and a single receptor in each preparation. 3 In the PCDA the α 1 ‐adrenoceptor antagonists, prazosin (0.01–1 μ m ) and YM‐12617 (0.01–1μ m ) produced non‐parallel rightwards shifts in the CRC to noradrenaline, with the lower 10–15% of the CRC exhibiting greater resistance to the effects of these antagonists compared to the upper part. In contrast, rauwolscine (1–10 μ m ) and CH‐38083 (10 μ m ) produced parallel displacement of the CRC to noradrenaline. In the PLV, low concentrations of either α 1 ‐ (0.01 μ m ) or α 2 ‐adrenoceptor antagonists (0.1–1 μ m ) produced a large shift in the CRC, but subsequent higher concentrations had only small additional effects. Based upon p K B values estimated from the effects of the lower concentrations of antagonists, the results are consistent with a large population of α 1 ‐adrenoceptors in the PCDA and a mixture of α 1 ‐ and α 2 ‐adrenoceptors in the PLV. 4 In both tissues, when an α 1 ‐ and an α 2 ‐adrenoceptor antagonist were used in combination the effect produced was greater than that with either agent alone. In contrast, the combination of the α 1 ‐adrenoceptor antagonists (prazosin and YM‐12617 together) or the α 2 ‐adrenoceptor antagonists (CH‐38083 and rauwolscine together) were no more effective than that produced by the individual antagonists. These findings suggest the presence of functional α 1 ‐ and α 2 ‐adrenoceptors in the PLV and PCDA. 5 Phenoxybenzamine (0.3–3 μ m , 60 min exposure) produced a concentration‐dependent reduction in the maximal response to noradrenaline which was more pronounced in the PCDA than the PLV. After a 60 min exposure to a combination of phenoxybenzamine (1 μ m ) and rauwolscine (1 μ m ), the remaining NA‐induced contraction after washout was resistant to prazosin (0.1 μ m ) and sensitive to rauwolscine (1 μ m ) in both tissue preparations, indicating the existence of functional α 2 ‐adrenoceptors in both vessels. 6 Evidence suggests that post‐junctional α 1 ‐ and α 2 ‐adrenoceptors contribute to noradrenaline‐induced contractions in the PCDA and PLV, with the latter possessing a larger population of functional α 2 ‐adrenoceptors.