Postjunctional α‐adrenoceptors in the rabbit isolated distal saphenous artery: indirect sensitivity to prazosin of responses to noradrenaline mediated via postjunctional α2‐adrenoceptors

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Abstract
1 Under normal experimental conditions, the rabbit isolated distal saphenous artery appears to contain a homogeneous population of postjunctional α1-adrenoceptors. Prazosin competitively antagonized responses to noradrenaline (NA) with a pA2 value of 8.6, while a relatively high concentration of rauwolscine (1 μm), produced only a 2 fold rightward displacement of the NA cumulative concentration-response curve (CCRC). 2 Despite the fact that angiotensin II (AII) was without effect on responses to NA or phenylephrine in this preparation, this peptide made responses to NA less susceptible to the antagonistic action of prazosin. This was particularly evident on the lower portion of the CCRC for NA. These results suggest that in the presence of AII, NA produces contractile responses by an action mediated through a prazosin-resistant adrenoceptor. 3 An attempt was made to isolate a homogeneous population of postjunctional α2-adrenoceptors by use of a receptor protection procedure involving the combination of rauwolscine and phenoxybenzamine. After the protection protocol no responses were observed to the α-adrenoceptor agonists NA, phenylephrine or UK-14304. In the presence of angiotensin II however, concentration-dependent contractions were observed to each of these agonists. Under these conditions the rank order of potency, UK-14304 > NA > phenylephrine, is consistent with that of an effect mediated through postjunctional α2-adrenoceptors. 4 The responses to NA, after the protection protocol, in the presence of AII, were susceptible to the selective α2-adrenoceptor antagonist, rauwolscine (1 μm), but resistant to the selective α1-adrenoceptor antagonist prazosin (0.1 μm). Furthermore, the combination of rauwolscine (1 μm) and prazosin (0.1 μm) was no more effective in blocking responses to NA than was rauwolscine (1 μm) alone. These results are consistent with the presence of a homogeneous population of postjunctional α2-adrenoceptors. 5 Inducing a small degree of tone with a low concentration of the selective α1-adrenoceptor agonist, phenylephrine, markedly increased the threshold sensitivity to the selective α2-adrenoceptor agonist UK-14304, in a manner analogous to that seen with AII. 6 The results in the present study indicate that responses mediated via postjunctional α2-adrenoceptors in the rabbit isolated distal saphenous artery are dependent upon a degree of vascular smooth muscle stimulation by some other receptor system. It is hypothesized that under normal experimental conditions, this function is fulfilled by stimulation of α1-adrenoceptors, while after α1-adrenoceptor blockade the necessary positive influence can be provided by stimulation of AII receptors. The implications for such an interaction between postjunctional α-adrenoceptor subtypes in demonstrating prazosin-resistant, rauwolscine- or yohimbine-sensitive responses in isolated blood vessels is discussed.