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

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2010-12, Vol.382 (5-6), p.487-497
• Main Authors: Jantschak, Florian, Popp, Alexander M., Hofmann, Raik A., Villalón, Carlos M., Centurión, David, Pertz, Heinz H.
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-2 Receptor Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; Animals; Arteries - drug effects; Arteries - physiology; Biomedical and Life Sciences; Biomedicine; Brimonidine Tartrate; Dioxanes - pharmacology; Imidazoles - pharmacology; In Vitro Techniques; Isoindoles - pharmacology; Isoquinolines - pharmacology; Male; Mice; Mice, Inbred C57BL; Neurosciences; Original Article; Pharmacology/Toxicology; Piperazines - pharmacology; Prazosin - pharmacology; Quinolizines - pharmacology; Quinoxalines - pharmacology; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-2 - physiology; Serotonin - pharmacology; Tail - blood supply; Temperature; Vasoconstriction - drug effects; Vasoconstriction - physiology; Yohimbine - pharmacology
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-010-0564-z

The isolated rat tail artery (RTA) represents an in vitro model of the cutaneous circulation. We have characterised the postjunctional α 2 -adrenoceptor subtype mediating vasoconstriction to the α 2 -adrenoceptor (α 2 -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 (pA 2  = 10.05 ± 0.07), rauwolscine (pA 2  = 8.82 ± 0.06), yohimbine (pA 2  = 8.45 ± 0.04), WB4101 (pA 2  = 8.05 ± 0.05), BRL44408 (pA 2  = 7.20 ± 0.04), ARC239 (pA 2  = 6.90 ± 0.05) and prazosin (pA 2  = 6.80 ± 0.05). Schild regressions were linear and had slopes of unity. Affinities (pA 2 ) for MK912, rauwolscine, yohimbine and WB41104 were in the same range as binding data (pK D ) for these drugs at α 2C -ARs of rat cerebral cortex. In addition, the presence of α 2C -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 pA 2  = 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 pA 2  = 8.80–8.90). The enhancement of the maximal UK14304 response was abolished by rewarming to 37°C. It is concluded that α 2C -ARs predominantly mediated vasoconstriction in RTAs at any temperature tested. Since α 2C -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.