Effects of cooling on α2‐adrenoceptor mediated contraction of rat tail vein

Abstract

a2‐Adrenoceptor (a2‐AR) mediated venous contraction plays an important role in thermoregulation. We investigated how cooling of rat tail vein, in vitro, affects a2‐AR mediated contraction. Tail veins were isolated, endothelium removed, and incubated at 37°C or 28°C for 2.5 hrs. At 37°C the a2‐AR agonist UK14304 caused contraction with an EC50 of 11.9 nM. Cooling to 28°C decreased the EC50 to 1.5 nM and increased maximal response by 46%. The same pattern was found with other a2‐AR agonists BHT933, guanabenz and dexmedetomidine; but not with 5‐HT, angiotensin II, arginine vasopressin, and phenylephrine. The affinities (KB's in nM) of a2‐AR antagonists determined from Schild plot were increased after cooling: RX821002 (non‐selective, 2 at 37°C, 0.2 at 28°C), MK912 (a2C‐AR selective, 0.1 at 37°C, 0.06 at 28°C), rawolscine (a2A/C‐AR selective, 11 at 37°C, 1 at 28°C), ARC239 (a2B‐AR selective, 181 at 37°C, 68 at 28°C). KB's for antagonists were consistent with the a2C‐AR subtype. UK14304 contraction was nearly eliminated by pertussis toxin at 37°C, however; pertussis toxin had little effect at 28°C. Cooling selectively increased α2C‐AR mediated contraction that may be due, in part, to increased affinity of α2C‐AR's and/or a change in α2C‐AR coupling to a Gi protein independent pathway. Thus the development of α2C‐AR selective agents may be useful to modulate venous function in diseases of altered thermoregulation.