1 The activities of the (-)-and (+ )-forms of m-and p-octopamine and m-and p-synephrine on a,-adrenoceptors from rat aorta and anococcygeus and a2-adrenoceptors from rabbit saphenous vein were compared with those of noradrenaline (NA).2 The rank order of potency of the (-)-forms on cx,-adrenoceptors from rat aorta and a2-adrenoceptors was NA > m-octopamine = m-synephrine > p-octopamine = p-synephrine. The two m-compounds were 6 fold less active than NA on x,-adrenoceptors from rat aorta and 150 fold less active on x,-adrenoceptors. The two p-compounds were 1,000 fold less active than NA on both oqadrenoceptors from rat aorta and x2-adrenoceptors. The rank order ofpotency ofthe (-)-forms on oqadrenoceptors from rat anococcygeus was NA = m-synephrine > m-octopamine >p-octopamine = p-synephrine. m-Octopamine was 4 fold less active than NA and (-)-m-synephrine. The two pcompounds were 30 fold less active than NA. 3 The rank order of potency of the (+)-forms was NA>m-octopamine>m-synephrine>p-octopamine >p-synephrine on both a,-and M2-adrenoceptors. The potency ofeach ( + )-form was 1-2 orders of magnitude less than that of the (-) counterpart, the differences being greater for the stereoisomers of synephrine than for those of octopamine on both a,-and M2-adrenoceptors. 4 The yohimbine diastereoisomer antagonists, rauwolscine and corynanthine, were tested against (-)-NA and (-)-m-octopamine-induced contractions in both preparations. Based upon the known selectivities of these isomers for a-adrenoceptor subtypes, it is concluded that the rat aorta contains only a,-adrenoceptors while the rabbit saphenous vein possesses predominantly M2-adrenoceptors.5 Ligand binding data for the octopamine and synephrine stereoisomers at oq-and a2-binding sites from rat cerebral cortex was also obtained. (-)-Forms were more active than (+ )-forms. The rank order of affinity of the (-)-forms for both a,-and M2-binding sites was NA > m-octopamine = msynephrine >p-synephrine >p-octopamine. The relative affinities ofthe members ofthe series against a,-binding sites were very similar to their relative functional activities on rat aorta. However, the affinities of both m-and p-compounds relative to that of ( -)-NA were much greater at the x2-binding sites than were the relative activities in rabbit saphenous vein, possibly suggesting low intrinsic efficacy. Functional antagonist responses to NA by the (-)-octopamine and synephrines could not, however, be demonstrated on rat aorta or rabbit saphenous vein. 6 The activities of m-octopamine and m-synephrine were not significantly different from each other on either a,-adrenoceptors from rat aorta or x2-adrenoceptors; however, m-synephrine is more active than m-octopamine on a,-adrenoceptors from rat anococcygeus. Both m-octopamine and msynephrine can be considered to be naturally occurring x,-selective amines. However, if m-and poctopamine are co-released with NA in amounts proportional to their concentration, it is concluded that their activities on m,-and x2-adrenoceptors are too low to be ...

1The influence of blood gases on a-and a2-adrenoceptor-mediated pressor responses was studied in the pithed rat by varying the inspired gas mixture or the ventilation stroke volume. 2 Acidosis favoured the peak responses to the m2-adrenoceptor agonist, xylazine, while alkalosis favoured the peak responses to the a,-adrenoceptor agonist, phenylephrine. A combination of hypoxia and hypercapnia greatly depressed the ml response to phenylephrine whereas the M2 response to xylazine remained relatively unaffected. 3 When Pao2 was varied in either acidotic or alkalotic conditions the response to the phenylephrine increased as Pao2 increased. 4 To prevent hypoxia in air ventilated rats, large stroke volumes were required. This caused alkalosis and hence decreased responsiveness to xylazine. Consequently, air ventilated pithed rats gave poorer responses to xylazine than did those ventilated on 100% 02. 5 The results show that ml-and a2-adrenoceptor-mediated pressor responses can be differentially affected by blood gases. The relative contribution of al-and M2-adrenoceptors to vascular tone may be either under-or over-estimated depending on the arterial blood gases.

1 Nifedipine was tested against pressor responses in the pithed rat to ten agonists with varying selectivity for a,-and a2-adrenoceptors, injected as a bolus or infused intravenously: i.e. amidephrine, azepexole, cirazoline, indanidine, M7, methoxamine, noradrenaline (NA), oxymetazoline, phenylephrine and xylazine. Nifedipine, administered before the agonists, inhibited responses initiated by all agonists, usually for both the bolus and infusion responses. 2 With a bolus, blockade was significantly greater against the more prolonged, secondary components of the pressor responses. This demonstrates that calcium-entry occurs during the secondary component of the a-adrenoceptor-mediated response and can be initiated by either a,-or 2-adrenoceptor subtypes.3 The time courses of responses to infusion varied. Selective a,-adrenoceptor agonists, with the exception of indanidine, did not produce a stable pressor response during the 20 min infusion time but M2-adrenoceptor agonists did. Nifedipine reduced responses to infusion with no preference for a,-or a2-agonists. Phenylephrine and NA produced pressor responses which reached a peak and then declined during the remainder of the infusion. 4 The levels ofNA in arterial and venous plasma were measured by h.p.l.c. during the infusion ofNA. Arterial NA levels rose throughout the infusion whereas venous levels remained relatively unaffected. The absolute levels of plasma NA suggest that a large proportion of intravenously administered NA is removed in the pulmonary circulation and the remainder is removed in the systemic circulation with negligible recirculation. 5 The consequences of these results, for assessment of the mechanisms of action of adrenoceptor agonists and calcium entry blockers, are discussed.