SUBTYPES OF α1-ADRENOCEPTORS IN RABBIT SAPHENOUS VEIN

We investigated the a,-adrenoceptor subtypes of rabbit saphenous vein which has a mixed functional population of α1 and α2 -adrenoceptors. Lateral saphenous veins were obtained from male rabbits weighing 3.20-4 kg, which were killed by overdose with pentobarbitone sodium (i.v. injection). They were easily dissected out and placed in cold, oxygenated modified Krebs-Henselite solution (Krebs). Each preparation was cut transversely into 3-4 mm rings and suspended between thick wire supports. The vein rings were mounted in 10 mL isolated organ bath, bathed in Krebs maintained at 37°C and gassed with 95% 02 plus 5% CO2, Cumulative concentration-response curves (CCRC) were constructed by increasing the concentration of the agonists in half-log increments. The preparations were left for a further period of 45-60 min before re-exposure to the agonist. Competitive antagonists like prazosin and rauwolscine were incubated in preparations at least for 45 minutes prior to the onset of a second CCRC. The strategy was based on using the a1-adrenoceptor selective agonist, phenylephrine (PE). Prazosin, an α1 -adrenoceptor selective antagonist, competitively inhibited contractile responses to phenylephrine with a pA2 value of 8, WB-41 0 1 had a pA2 of 8.6 but a low Schild plot slope, while low potency was found with 5MU (PA2 7.2) and HV -723 (pA2 7.97). This data is not consistent with a definitive for αlA or αlN and taken alone the evidence from prazosin is in favour of αIL' However the selective α2- adrenoceptor antagonist delequamine inhibited phenylephrine-induced contractions. Overall the data is consistent with phenylephrine-induced contractions being mediated by a,- and a2 -adrenoceptors. The best estimate of the subtype of ajadrenoceptor mediating contraction is aiL due to the relatively low absolute pA2 values for prazosin.