The role of α 2 ‐adrenoceptors in the vasculature of the rat tail

1 The effects of α 2 ‐adrenoceptor agonists and antagonists on rat tail skin temperature (t ts ), an indicator of local cutaneous blood flow, were studied in conscious and anaesthetized rats and in the isolated, Krebs perfused, vascular bed of the rat tail. 2 In conscious rats, at an ambient temperature of 18.5–20°C, t ts was 21.0 ± 0.2°C and core (rectal) temperature (t c ) was 38.2 ± 0.04°C (n = 126). The α 2 ‐adrenoceptor antagonist, delequamine (RS‐15385‐197; 1 mg kg −1 , s.c., n = 6), produced a rapid elevation in t to 29.1 ± 0.7°C (P < 0.001 vs . saline‐treated control group), attained 10 min after injection. t c fell slightly, by 1.0 ± 0.1°C. The t ts response was dose‐related over the dose‐range tested (0.01‐1 mg kg ‐1 , s.c.), with an ED 50 of 17 μg kg 1 , s.c. (n =6 per dose). 3 The maximum increases in t ts in response to a dose of 1 mg kg ‐1 , s.c. of α 2 ‐adrenoceptor antagonists were as follows (n = 6 per drug): delequamine (+ 9.6 ± 0.8°C)> yohimbine (+ 9.0 ± 1.0°C)> WY‐26703 (+ 7.9 ± 1.3°C) > piperoxan (+ 5.6 ± 1 7°C) > idazoxan (+ 4.6 ± 1.3°C) > imiloxan (+ 4.1 ± 1.3°C) > SKF 104078 (+2.0 ± 1.9°C)>BDF‐6143 (+1.3 ± 0.8°C). 4 Prazosin (0.3mg kg ‐1 , s.c.), hydralazine (10mg kg ‐1 , s.c.) and nifedipine (3mg kg ‐1 , s.c.) did not increase t ts , whereas propranolol (10mg kg ‐1 , s.c.) evoked a small increase in t ts (+2.9 ± 1.0°C). Pentolinium (2–10 mg kg −1 , s.c.) elicited a dose‐related increase in t ts which was elevated by 4.4 ± 1.3°C after a dose of 10 mg kg −1 ; t c was reduced in a dose‐related manner. Drug vehicles (1 ml kg −1 , s.c) had no effect on t te or t c . 5 In anaesthetized rats, idazoxan (300 μg, i.v.) produced a rapid increase in t ts which was detectable 2 min after beginning the injection, reaching a peak after 7 min. When the same dose was administered i.c.v., t ts also rose, but more slowly. The peak response (+ 3.6 ± 0.7°C, n = 5) was significantly smaller than when idazoxan was administered intravenously (+6.3± 1.2°C, n = 5), which suggests that the increase in t ts following systemic administration of α 2 ‐adrenoceptor antagonists is not due to a central effect. The change in t ts was not secondary to changes in blood pressure. 6 In the isolated, Krebs perfused, tail vascular bed of the rat, at an ambient temperature of 20–21°C, under constant flow conditions (3.5‐4.0 ml min −1 ; n = 4), baseline perfusion pressure was 57 ± 4 mmHg. 5‐Hydroxytryptamine (5‐HT; 70–150 nm) increased perfusion pressure by 56 ± 9 mmHg. The α 2 ‐adrenoceptor agonist, UK‐14,304 (10 nmol), elicited a further increase in perfusion pressure by 27.5 ± 15 mmHg but had no effect in the absence of 5‐HT; this response to UK‐14,304 was abolished by rauwolscine (1 μm). 7 Under constant pressure conditions (∼100 mmHg; n = 9), baseline mean perfusion flow was 2.1 ± 0.2 ml min −1 , and mean tail skin temperature was 31.6 ± 0.6°C. 5‐HT (119 ± 28 nM) decreased. t ts by 3.3 ± 2.0°C and reduced flow by 1.2 ± 0.3 ml min −1 . UK‐14,304 (10 nmol) further reduced t ts by 3.0 ± 0.3°C without significant effect on flow; this effect was also abolished by 1 μm rauwolscine. 8 We conclude that post‐junctional α 2 ‐adrenoceptors in the vasculature of the rat tail have a major vasoconstrictor role, controlling both the flow and distribution of blood within the tail and thereby thermoregulatory heat loss from its surface.