Gen. Pharmac. Vol. 22, No. 2, pp. 341-346, 1991 0306-3623/91 $3.00+ 0.00 Printed in Great Britain.All rights reserved Copyright© 1991 PergamonPresspie ALPHA1- AND ALPHA2-ADRENERGIC RESPONSE IN HUMAN ISOLATED SKIN ARTERIES DURING COOLING B. G6MEZ, J. BORBUJO, l A. L. GARCtA-VILLAL6N, E. NAvA-HERN~NDEZ,J. VALLE, J. L. GARCiA and G. Dr~GtmZ* Departamento de Fisiologia and ~Servicio de Dermatologia (Hospital La Paz), Facultad de Medicina, Universidad Aut6noma, 28029 Madrid, Espgna [Fax 3150075] (Received 9 July 1990) Ak~tract--l. Dose-response curves for noradrenaline, phenylephrine and clonidine were determined isometrically in 2-ram cylindrical segments from human skin arteries at 24°C and compared to those previously reported at 37°C. 2. Noradrenaline (3 × 10-z°-3 × 10-4 M) induced dose-dependent contraction and the sensitivity was increased during cooling. Phentolamine (10 -6 M), prazosin (10-6 M) or yohimbine (10 -6 M) produced a higher rightward shift of the control curve for noradrenaline during cooling. 3. Phenylephrine (10-H-3 × 10-4 M) and clonidine (10-H-10 -6 M) caused dose-dependent contraction and the sensitivity of the arteries was augmented at 24°C. 4. The arteries also showed a lower maximal contraction to the adrenergic agonists used and KCI (50 mM) during cooling. 5. The results suggest that cooling: (a) increases sensitivity of postjunctional ~l- and ~2-adrenoceptors in human skin arteries and (b) depresses contractility of these arteries to ~-adrenergic stimulation and direct activation of vascular smooth muscle. INTRODUCTION The primary function of skin blood flow is body temperature regulation and cutaneous circulation is largely controlled by the sympathetic vasoconstrictor system. It appears that cutaneous arteries and veins are equipped with a mixed population of postjunc- tional alphaz- and alpha2-adrenoceptors (De Mey and Vanhoutte, 1980; Stevens and Moulds, 1981; Flavahan et al., 1984; Steen et al., 1984; Flavahan and Vanhoutte, 1986a, Lindblad and Ekenvall, 1986; Steen et al., 1986; Flavahan et al., 1987; Nielsen et al., 1989) and both subtypes of alpha adrenoceptors mediate vasoconstrictor responses when are activated by the sympathetic neurotransmitter. It appears that temperature affects vascular con- tractility and adrenergic mechanisms in blood vessel wall. Cooling depressed the contractile response by direct activation of vascular smooth muscle with KCI or BaCI2 and this effect is not specific for cutaneous blood vessels but has also been found in other vascular beds (Vanhoutte, 1980; Vanhoutte and Flavahan, 1986). With regard to the adrenergic mechanisms, experimental observations (De Mey and Vanhoutte, 1980) indicate that moderate cooling increases the contractile response by sympathetic nerve stimulation and by exogenous noradrenaline in saphenous (cutaneous) vein but depresses the responses by this type of stimuli in femoral (deep) vein. This suggests that both the excitatory or inhibitory effects by cooling on adrenergic stimulation are exerted postjunctionaUy at the alpha- adrenoceptor. However, the role played by the alpha~ and alpha2 adrenoceptors in the excitatory effect by *To whom correspondence should be addressed. cooling on the adrenergic response of cutaneous blood vessels remains inconclusive and most of studies has been performed in the canine saphenous vein (Janssens et al., 1981; Flavahan et al., 1985; Vanhoutte and Flavahan, 1986). Studies on the effects of temperature on adrenergic response in cutaneous arterial bed are scanty and the available results are not clear (Keatinge, 1958; Glover et al., 1968; Patton and Wallace, 1978; Kroeger et al., 1985). Since tissue blood flow is mainly regulated at the arterial bed the study of the effects of cooling on the adrenergic response in cutaneous arteries could be of interest. In our laboratory we have recently ob- served that the adrenergic constriction of skin arteries of humans is mediated by both postjunctional alpha l- and alpha2-adrenoceptors and that this vasoconstric- tion appears to rely predominantly on the alpha2- adrenoceptors (Borbujo et al., 1989). The aim of the present work was to analyze the effects of moderate cooling on the reactivity of human skin arteries to alpha adrenergic activation as well as the role played by the alpha1- and alpha2-adrenoceptors in these effects. The experiments were performed isometrically in isolated arteries at 24°C and the results are com- pared with those referred previously to this type of arteries at 37°C (Borbujo et al., 1989). MATERIALS AND METHODS To carry out the present experiments, subcutaneous arteries were obtained from 12 patients (36 to 74 year old) who had died 3 to 12 hr before and did not show peripheral arterial disease. At the autopsy, a piece of abdominal skin with subcutaneous tissue attached was removed. The arteries were then carefully dissected free and cut into cylindrical segments 2 mm in length and approximately 900 #m in external diameter. 341