Article date: February 1995
By: N.A. Blaylock, V.G. Wilson, in Volume 114, Issue 3, pages 694-702
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 α1‐adrenoceptor antagonists) or rauwolscine and CH‐38083 (selective α2‐adrenoceptor antagonists).
Noradrenaline (0.003–10 μm) produced concentration‐dependent contractions in both vessels, with the PCDA (pD2 = 6.33 ± 0.07, n = 10) being approximately 10 fold less sensitive to noradrenaline compared to the PLV (pD2 = 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 μm) produced parallel rightward shifts in the CRC to noradrenaline in both tissue preparations. The pA2 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.
In the PCDA the α1‐adrenoceptor antagonists, prazosin (0.01–1 μm) and YM‐12617 (0.01–1μm) 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 μm) and CH‐38083 (10 μm) produced parallel displacement of the CRC to noradrenaline. In the PLV, low concentrations of either α1‐ (0.01 μm) or α2‐adrenoceptor antagonists (0.1–1 μm) produced a large shift in the CRC, but subsequent higher concentrations had only small additional effects. Based upon pKB values estimated from the effects of the lower concentrations of antagonists, the results are consistent with a large population of α1‐adrenoceptors in the PCDA and a mixture of α1‐ and α2‐adrenoceptors in the PLV.
In both tissues, when an α1‐ and an α2‐adrenoceptor antagonist were used in combination the effect produced was greater than that with either agent alone. In contrast, the combination of the α1‐adrenoceptor antagonists (prazosin and YM‐12617 together) or the α2‐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 α1‐ and α2‐adrenoceptors in the PLV and PCDA.
Phenoxybenzamine (0.3–3 μm, 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 μm) and rauwolscine (1 μm), the remaining NA‐induced contraction after washout was resistant to prazosin (0.1 μm) and sensitive to rauwolscine (1 μm) in both tissue preparations, indicating the existence of functional α2‐adrenoceptors in both vessels.
Evidence suggests that post‐junctional α1‐ and α2‐adrenoceptors contribute to noradrenaline‐induced contractions in the PCDA and PLV, with the latter possessing a larger population of functional α2‐adrenoceptors.
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 α1‐adrenoceptor antagonists) or rauwolscine and CH‐38083 (selective α2‐adrenoceptor antagonists).
Noradrenaline (0.003–10 μm) produced concentration‐dependent contractions in both vessels, with the PCDA (pD2 = 6.33 ± 0.07, n = 10) being approximately 10 fold less sensitive to noradrenaline compared to the PLV (pD2 = 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 μm) produced parallel rightward shifts in the CRC to noradrenaline in both tissue preparations. The pA2 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.
In the PCDA the α1‐adrenoceptor antagonists, prazosin (0.01–1 μm) and YM‐12617 (0.01–1μm) 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 μm) and CH‐38083 (10 μm) produced parallel displacement of the CRC to noradrenaline. In the PLV, low concentrations of either α1‐ (0.01 μm) or α2‐adrenoceptor antagonists (0.1–1 μm) produced a large shift in the CRC, but subsequent higher concentrations had only small additional effects. Based upon pKB values estimated from the effects of the lower concentrations of antagonists, the results are consistent with a large population of α1‐adrenoceptors in the PCDA and a mixture of α1‐ and α2‐adrenoceptors in the PLV.
In both tissues, when an α1‐ and an α2‐adrenoceptor antagonist were used in combination the effect produced was greater than that with either agent alone. In contrast, the combination of the α1‐adrenoceptor antagonists (prazosin and YM‐12617 together) or the α2‐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 α1‐ and α2‐adrenoceptors in the PLV and PCDA.
Phenoxybenzamine (0.3–3 μm, 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 μm) and rauwolscine (1 μm), the remaining NA‐induced contraction after washout was resistant to prazosin (0.1 μm) and sensitive to rauwolscine (1 μm) in both tissue preparations, indicating the existence of functional α2‐adrenoceptors in both vessels.
Evidence suggests that post‐junctional α1‐ and α2‐adrenoceptors contribute to noradrenaline‐induced contractions in the PCDA and PLV, with the latter possessing a larger population of functional α2‐adrenoceptors.
DOI: 10.1111/j.1476-5381.1995.tb17194.x
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