No abstract

1 The isometric response to arginine-vasopressin (10-1o 10-7 M) was studied in 2 mm long rabbit arterial segments isolated from several vascular beds (cutaneous, pial, renal, coronary, muscular, mesenteric and pulmonary). 2 Vasopressin induced contraction in central ear (cutaneous), basilar (pial), renal, coronary and saphenous (muscular) arteries, but had no effect in mesenteric and pulmonary arteries; the order of potency for the contraction was: ear > basilar > renal > coronary > saphenous arteries. 3 Treatment with the blocker of nitric oxide synthesis NG-nitro-L-arginine methyl ester (L-NAME; 106-I0-M) increased significantly (P< 0.05) the contraction to vasopressin in ear (148% of control), basilar (150% of control), renal (304% of control), coronary (437% of control) and saphenous (235% of control) arteries. Removal of the endothelium increased significantly (P<0.05) the contraction to vasopressin in basilar (138% of control), renal (253% of control), coronary (637% of control) and saphenous (662% of control) arteries, but not in ear artery. Mesenteric and pulmonary arteries in the presence of L-NAME or after endothelium removal did not respond to vasopressin, as occurred in control conditions. 4 The specific antagonist for V1 vasopressin receptors d(CH2)5Tyr(Me)AVP (3 x 10-9-10-7 M) was more potent (pA2=9.3-10.1) than the antagonist for both VI and V2 vasopressin receptors desGly-d(CH2)5-D-Tyr(Et)ValAVP (10-7-10-6 M) (pA2 =7.4-8.4) to block the contraction to vasopressin of ear, basilar, renal and coronary arteries. 5 The specific V2 vasopressin agonist [deamino-Cys1, D-Arg8]-vasopressin (desmopressin) (10-1o-10-7 M) did not produce any effect in any of the arteries studied, with or without endothelium. 6 In arteries precontracted with endothelin-1, vasopressin or desmopressin did not produce relaxation. 7 These results suggest: (a) most arterial beds studied (5 of 7) exhibit contraction to vasopressin with different intensity; (b) the vasoconstriction to this peptide is mediated mainly by stimulation of V1 vasopressin receptors, and (c) endothelial nitric oxide may inhibit the vasoconstriction to this peptide, especially in coronary and renal vasculatures.

1 The role of the endothelium in the effects of cooling on the response to cholinoceptor stimulation of the rabbit central ear (cutaneous) and femoral (non-cutaneous) arteries was studied using 2 mm long cylindrical segments.2 Concentration-response curves for acetylcholine (I0-9-IO-OM), methacholine (10-9-1iO-M) and sodium nitroprusside (IO-9-IO-4M) were isometrically recorded in arteries under conditions, with and without endothelium or following pretreatment with the nitric oxide-synthesis inhibitor N0-nitro-Larginine methyl ester (L-NAME, 10-6-3 x 10-M) at 37°C and at 24°C (cooling). 3 Ear and femoral arteries showed endothelium-dependent relaxation to acetylcholine and methacholine at 37°C and 24°C. The extent of relaxation of the control ear arteries, but not of the control femoral arteries, to acetylcholine and methacholine increased during cooling. 4 L-NAME (10-6-3 x IO-4 M) reduced in a concentration-dependent way the response of ear arteries to acetylcholine at both 37°C and 24°C, this reduction being more potent at 37°C. L-Arginine (10-'-10-M) reversed in a concentration-dependent manner the inhibitor effects of 10-5 M L-NAME at both temperatures. 5 Sodium nitroprusside caused a concentration-dependent relaxation in both arteries that was endothelium-independent. However, the extent of relaxation to this nitrovasodilator in ear and femoral arteries was lower at 24°C. 6 These results suggest that cooling augments the reactivity of cutaneous (ear) arteries, but not that of non-cutaneous (femoral) arteries to cholinoceptor stimulation by endothelium-mediated mechanisms. Cooling could therefore facilitate the stimulated release of endothelial nitric oxide in cutaneous vessels.

1 Urocortin, an endogenous peptide structurally related to corticotropin-releasing factor (CRF), has potent cardiovascular e ects, suggesting that it may be of signi®cance in cardiovascular regulation. The objective of this study was to analyse the e ects of urocortin and its action mechanisms on human blood vessels. 2 To this, 3 mm long segments from human saphenous veins were prepared for isometric tension recording in an organ bath. 3 In the segments at basal resting tone, urocortin did not produce any e ect, but in the segments precontracted with endothelin-1 (1 ± 10 nM), urocortin (1 pM ± 10 nM) produced concentrationdependent relaxation. 4 This relaxation was not modi®ed by the inhibitor of nitric oxide synthase N G -nitro-L-arginine methyl ester (L-NAME, 100 mM), but it was potentiated by the cyclo-oxygenase inhibitor meclofenamate (10 mM) and it was reduced by the inhibitors of high-conductance Ca 2+ -dependent potassium channels tetraethylammonium (TEA, 10 mM) and charybdotoxin (100 nM). 5 These results indicate that human saphenous veins are very sensitive to urocortin, which produces vascular relaxation by a mechanism independent of nitric oxide and dependent of highconductance Ca 2+ -dependent potassium channels, and that it may be opposed by the release of vasoconstrictor prostanoids. Therefore, urocortin may be of signi®cance for regulation of the venous circulation in humans. British Journal of Pharmacology (2002) 136, 90 ± 94

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 degrees C and 24 degrees C (cooling). Under resting tension, both types of arteries contracted to histamine (10(-7)-10(-3) M), and the sensitivity of ear arteries, but not of femoral arteries was lower at 24 than at 37 degrees C. Chlorpheniramine (10(-7) M) blocked the contraction of both types of arteries to histamine at both temperatures. In ear arteries, endothelium removal or treatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10(-5) M) did not affect the contraction to histamine at 37 degrees C, but it reversed the decreased contraction at 24 degrees C. In femoral arteries, endothelium removal or L-NAME (10(-5) M) did not affect the response to histamine at 37 and 24 degrees C. Ear and femoral arteries precontracted with endothelin-1 (10(-8)-10(-7) M) and pretreated with chlorpheniramine (10(-5) M) relaxed to histamine (10(-7)-10(-4) M), and the sensitivity of this relaxation in ear arteries, but not in femoral arteries, increased at 24 degrees C. The relaxation of ear and femoral arteries to histamine was not modified by endothelium removal, L-NAME (10(-5) M) or meclofenamate (10(-5) M), but it was blocked by cimetidine (10(-6) M) at 37 degrees C and 24 degrees C. These results suggest: (1) ear and femoral arteries have contracting H1 and relaxing H2 receptors, probably located on smooth musculature, and (2) cooling reduces the contraction and increases the relaxation of cutaneous arteries to histamine: the reduction of this contraction could be caused by an augmented availability of endothelial nitric oxide, and the increment of this relaxation could be caused by an augmented sensitivity of H2 receptors of smooth musculature induced by cooling. These features do not seem to occur in deep vessels.