Silent α2C-adrenergic receptors enable cold-induced vasoconstriction in cutaneous arteries

被引:197
作者
Chotani, MA
Flavahan, S
Mitra, S
Daunt, D
Flavahan, NA
机构
[1] Ohio State Univ, Heart & Lung Inst, Med Res Facil, Columbus, OH 43210 USA
[2] Stanford Univ, Dept Comparat Med, Stanford, CA 94305 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2000年 / 278卷 / 04期
关键词
Raynaud's Phenomenon; scleroderma; microcirculation; thermoregulation; vascular smooth muscle;
D O I
10.1152/ajpheart.2000.278.4.H1075
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cold constricts cutaneous blood vessels by increasing the reactivity of smooth muscle alpha(2)-adrenergic receptors (alpha(2)-ARs). Experiments were performed to determine the role of alpha(2)-AR subtypes (alpha(2A-), alpha(2B-), alpha(2C-)ARS) in this response. Stimulation of alpha(1)-ARs by phenylephrine or alpha(2)-ARs by UK-14,304 caused constriction of isolated mouse tail arteries mounted in a pressurized myograph system. Compared with proximal arteries, distal arteries were more responsive to aa-AR activation but less responsive to activation of alpha(1)-ARs. Cold augmented constriction to alpha(2)-AR activation in distal arteries but did not affect the response to al-AR stimulation or the level of myogenic tone. Western blot analysis demonstrated expression of a(2A-) and alpha(2C-)ARs in tail arteries: expression of alpha(2C)-ARs decreased in distal compared with proximal arteries, whereas expression of the glycosylated form of the alpha(2A)-AR increased in distal arteries. At 37 degrees C, alpha(2)-AR-induced vasoconstriction in distal arteries was inhibited by selective blockade of alpha(2A)-ARS (BRL-44408) but not by selective inhibition of alpha(2B)-ARs (ARC-239) or alpha(2C)-ARs (MK-912). In contrast, during cold exposure (28 degrees C), the augmented response to UK-14,304 was inhibited by the alpha(2C)-AR antagonist MK-912, which selectively abolished cold-induced amplification of the response. These experiments indicate that cold-induced amplification of alpha(2)-ARs is mediated by alpha(2C)-ARs that are normally silent in these cutaneous arteries. Blockade of alpha(2C)-ARs may prove an effective treatment for Raynaud's Phenomenon.
引用
收藏
页码:H1075 / H1083
页数:9
相关论文
共 53 条
[1]  
BOEGE F, 1988, J BIOL CHEM, V263, P9040
[2]  
BYLUND DB, 1994, PHARMACOL REV, V46, P121
[3]   Homologous regulation of the α2C-adrenoceptor subtype in human hepatocarcinoma, HepG2 [J].
Cayla, C ;
Schaak, S ;
Roquelaine, C ;
Gales, C ;
Quinchon, F ;
Paris, H .
BRITISH JOURNAL OF PHARMACOLOGY, 1999, 126 (01) :69-78
[4]  
COFFMAN JD, 1990, J VASC MED BIOL, V2, P100
[5]  
COUPRY I, 1992, J BIOL CHEM, V267, P9852
[6]   Subtype-specific intracellular trafficking of alpha(2)-adrenergic receptors [J].
Daunt, DA ;
Hurt, C ;
Hein, L ;
Kallio, J ;
Feng, F ;
Kobilka, BK .
MOLECULAR PHARMACOLOGY, 1997, 51 (05) :711-720
[7]  
DUZIC E, 1992, J BIOL CHEM, V267, P24045
[8]   ALPHA-ADRENOCEPTORS AND COLD-INDUCED VASOCONSTRICTION IN HUMAN FINGER SKIN [J].
EKENVALL, L ;
LINDBLAD, LE ;
NORBECK, O ;
ETZELL, BM .
AMERICAN JOURNAL OF PHYSIOLOGY, 1988, 255 (05) :H1000-H1003
[9]   EFFECT OF LOCAL TISSUE COOLING ON MICROVASCULAR SMOOTH-MUSCLE AND POSTJUNCTIONAL ALPHA-2-ADRENOCEPTORS [J].
FABER, JE .
AMERICAN JOURNAL OF PHYSIOLOGY, 1988, 255 (01) :H120-H130