Acla Physiol Scand 1994. 151,441-451 Cooling effects on the histaminergic response of rabbit ear and femoral arteries: role of the endothelium N. FERNANDEZ,' A. L. GARCiA-VILLALON,' j. BORBU]O,2 L. MONGE,' J L. GARCIA,' B. GOMEZ' and G. DIEGUEZ' IDepanamento de Fisiologia and 2Serv icio de Dermatologia (Hospiral La Paz), Universidad Auronoma de Madrid, Spain N. FERNANDEZ, A. L GARdA-VILLALON, J. BORBU]O, L. MONGE, J. L. GARciA, B. GOMEZ & G. DIEGUEZ. 1994. Cooling effects on (he histaminergic response of rabbit ear and femoral arteries. Role of the endothelium. Acta Physiol Scand 151, 441-45 l. Received 10 ber 1993, accepred 4 March 1994. ISSN 0001-6774. Departamenro de Fisiologla, Universidad Auronoma de Madrid, Spain. The effects of cooling on the isometric response of rabbit isolated central ear (cutaneous) and femoral (non-cutaneous) arteries to histamine were determined at 37°C and 24 <:IC (cooling). Under resting rension. bOlh types of arteries conrracted ro histamine (10- 1 -10- 3 M), and the sensitivity of ear arteries. but nOt of femoral arteries was lower at 24 than at 37 0e. Chlorpheniramine (10- 7 M) blocked the contraction of both types of arteries fO histamine at both remperatures. In ear arteries. endorhelium removal or treatment with the nitric oxide synthase inhibitor methyl ester (L- N AME, M) did not a ff'ect the contraction to histamine at 37 °e, but it reversed the decreased contraction at 24°e. In femoral arteries, endothelium removal or L-NAME (l0-£> M) did not affect the response to histamine at 37 and 24°e. Ear and femoral arteries precomracred wilh endorhelin-I (10-&-10- 7 M) and pretreated with chlor- pheniramine M) relaxed to histamine (10-'-10·'4 M), and the sensitivity of this relaxation in ear arteries, but not in femoral arteries, increased at 24 <:Ie. The relaxation of ear and femoral arteries to histamine was nor modified by endothelium removal, L- NAME (10- 3 M) or meciofenamate (lO-!> M), but it was blocked by cimetidine (10- 6 M) at 37 o( and 24 0e. These results suggest: (I) ear and femoral arteries have contracting H t and relaxing H2 receptors, probably located on smooth musculature, and (2) cooling reduces rhe conrraction and increases the relaxation of cutaneous arteries to histamine: the reduction of this contraction could be caused by an augmented availability of endo(helial nitric oxide, and the increment of this relaxation could be caused by an augmented sensitivity of H9 receprors of smooth musculature induced by cooling. These features do not seem to occur in deep vessels. Key words.' cutaneous arteries, hisramine, nitric oxide, temperature. Histamine in humans and orher species produces arterial hypotension by decreasing total peri- pheral vascular resistance, which is mediated by histaminergic H, and H2 receptors distributed throughout the resistance vessels (Douglas 1985). I n isolated vessels, however, histamine can Correspondence: Angel Luis Garcia-Villalon, Departamento de Fisiologia, Facultad de Medicina, Universidad Aut6noma. Arzobispo Morcillo, 1,28029 Madrid, Spain. produce contraction or relaxation via stimulation of Hl and H2 receptors, respectively, and these effects depend upon the animal species and the type of blood vessel within a single species (Owen 1977, Douglas 1985). The role of the endothelium on the vascular effects to histamine is controversial (Toda 1990, Tayo 1991, Ortiz et al. 1992). With regard to cutaneous blood vessels it seems that histamine induces vasodilatation in the skin of the face and upper part of the body 441