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

Abstract

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.

Alpha2C-adrenoceptors play a prominent role in sympathetic constriction of porcine pulmonary arteries

“…5). The affinity (apparent pA 2 ) of 9.75 and 9.62 for 0.3 and 1 nM MK912, a competitive or noncompetitive antagonist in different studies, is in good agreement with that for this drug in porcine pulmonary veins, rat tail artery, and equine digital veins, tissues in which UK14304 contractions are mediated by the α 2C subtype (Görnemann et al 2007;Jantschak et al 2010;Zerpa et al 2010). The affinity (apparent pA 2 ) of 7.40 for BRL44408 (0.1 and 0.5 μM), which is inconsistent with the presence of α 2A -and α 2B -ARs (pK i 8.25, cloned human α 2A -ARs; pK i 6.19, cloned human α 2B -ARs; Uhlén et al 1994), is similar to that estimated in porcine pulmonary veins (7.02; Görnemann et al 2007).…”

“…An enhancement of responses can be achieved with KCl or G-protein-coupled receptor agonists such as prostaglandin F 2α , vasopressin, endothelin-1, serotonin, or angiotensin II (Harker et al 1991;Templeton et al 1989;MacLean and McGrath 1990;Redfern et al 1995;Schümann and Lues 1983). Recently, we could show that UK14304 (α 2 -AR agonist)-induced constriction of rat tail arteries precontracted with serotonin was mediated by α 2C -ARs (Jantschak et al 2010). It has been suggested that the uncovering of α 2 -AR-mediated vasoconstrictor responses by raising the vascular tone is due to an increase in [Ca 2+ ] i or an activation of the Rho kinase pathway (Chotani and Flavahan 2011).…”

“…As we identified contractile α 2C -ARs in porcine pulmonary veins (Görnemann et al 2007) and in precontracted rat tail arteries (Jantschak et al 2010), we now wanted to characterize (1) the role of Ca 2+ in α 2 -AR-mediated contractile responses in porcine pulmonary arteries and (2) the α 2 -AR subtype in this tissue. In our experiments, we used the L-type Ca 2+ channel activator (S)-(−)-Bay K 8644 (Schramm et al 1983) which serves as a more specific stimulus than KCl or agonists that activate receptors coupled to Gα q/11 and Gα 12/13 (Alvarez et al 2010).…”

Intracellular α2C-Adrenoceptors: Storage depot, stunted development or signaling domain?

“…through activation of RhoA/ROCK. Indeed, in the rat tail artery, which has only a weak α 2 -AR constrictor response [73, 82], responses to α 2 -AR activation were mediated by α 2C -ARs in the presence of a pre-constricting agent (serotonin) [83] but not when studied under basal conditions [84]. …”

Moderate hypothermia attenuates α1-adrenoceptor-mediated contraction in human varicose spermatic vein: The role of nitric oxide(Short communication)

“…Moderate hypothermia, cooling to 25-31°C, has been shown to have a variable influence on the vascular sensitivity to various drugs and endogenous substances in different parts of the vascular system of animals (5). We have previously studied the thermal responses of smooth muscle in various vessels and observed that the sensitivity of different agents were temperature dependent (2,11).…”