Postjunctional α2C-adrenoceptors mediate vasoconstriction in rat tail artery: influence of precontraction and temperature on vasoreactivity

The isolated rat tail artery (RTA) represents an in vitro model of the cutaneous circulation. We have characterised the postjunctional α2-adrenoceptor subtype mediating vasoconstriction to the α2-adrenoceptor (α2-AR) agonist UK14304 in RTA. In non-precontracted arterial rings at 32°C, a physiological temperature for the RTA, UK14304 elicited only slight contractions which were markedly enhanced after precontraction with serotonin (5-HT; 10–50 nM). Under the condition of elevated vascular tone, the contractile UK14304 response was competitively antagonised by MK912 (pA2 = 10.05 ± 0.07), rauwolscine (pA2 = 8.82 ± 0.06), yohimbine (pA2 = 8.45 ± 0.04), WB4101 (pA2 = 8.05 ± 0.05), BRL44408 (pA2 = 7.20 ± 0.04), ARC239 (pA2 = 6.90 ± 0.05) and prazosin (pA2 = 6.80 ± 0.05). Schild regressions were linear and had slopes of unity. Affinities (pA2) for MK912, rauwolscine, yohimbine and WB41104 were in the same range as binding data (pKD) for these drugs at α2C-ARs of rat cerebral cortex. In addition, the presence of α2C-ARs was confirmed by Western blotting. In experiments to study the influence of temperature on vasoreactivity, UK14304-induced contractions did not differ at 37°C, 32°C or 27°C and were similarly blocked by rauwolscine (apparent pA2 = 8.73–8.90). After rapid cooling (from 37°C to 27°C), the maximal UK14304 response was enhanced only in precontracted arteries; antagonism by rauwolscine was the same before and after cooling (apparent pA2 = 8.80–8.90). The enhancement of the maximal UK14304 response was abolished by rewarming to 37°C. It is concluded that α2C-ARs predominantly mediated vasoconstriction in RTAs at any temperature tested. Since α2C-ARs may be involved in Raynaud’s phenomenon, the isolated RTA represents a convenient in vitro bioassay to test novel compounds for the treatment of this syndrome.