Bergdahl A, Nilsson T, Sun X Y, Hedner T, Edvinsson L
Department of Internal Medicine, Lund University Hospital, Sweden.
Eur J Pharmacol. 1998 Nov 6;360(2-3):165-73. doi: 10.1016/s0014-2999(98)00655-4.
The aim of the present study was to elucidate if the potentiating effect of neuropeptide Y on various vasoactive agents in vitro is (1) altered in mesenteric arteries from rats with congestive heart failure and (2) mediated by the neuropeptide Y Y1 receptor. The direct vascular effects of neuropeptide Y and its modulating effects on the contractions induced by endothelin-1-, noradrenaline-, 5-hydroxytryptamine (5-HT)-, U46619-(9,11-dideoxy-11alpha, 9alpha-epoxymethano-prostaglandin F2alpha) and ATP, and acetylcholine-induced dilatations were studied in the presence and absence of the neuropeptide Y Y1 antagonist, BIBP3226 (BIBP3226¿(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl ]-D-arginine-amide¿). Neuropeptide Y, per se, had no vasoactive effect in the arteries. The potency of endothelin-1 was significantly decreased in congestive heart failure rats. Neuropeptide Y and neuropeptide Y-(13-36) potentiated the endothelin-1-induced contraction in congestive heart failure mesenteric arteries. In 20% of the congestive heart failure rats, sarafotoxin 6c induced a contraction of 31+/-4%. Neuropeptide Y also potentiated U46619- and noradrenaline-induced contractions but not 5-HT-induced contractions in congestive heart failure arteries. In sham-operated animals neuropeptide Y potentiated noradrenaline- and 5-HT-induced contractions. These potentiations were inhibited by BIBP3226. Acetylcholine induced an equipotent relaxation in both groups which was unaffected by neuropeptide Y. In conclusion, neuropeptide Y responses are altered in congestive heart failure rats. The potentiating effect differs between vasoactive substances. Neuropeptide Y Y1 and non-neuropeptide Y1 receptors are involved.
本研究的目的是阐明神经肽Y对多种血管活性物质的体外增强作用是否：（1）在充血性心力衰竭大鼠的肠系膜动脉中发生改变；（2）由神经肽Y Y1受体介导。在存在和不存在神经肽Y Y1拮抗剂BIBP3226（BIBP3226，(R)-N2-(二苯基乙酰基)-N-[(4-羟基苯基)甲基]-D-精氨酸酰胺）的情况下，研究了神经肽Y的直接血管效应及其对内皮素-1、去甲肾上腺素、5-羟色胺（5-HT）、U46619（9,11-二脱氧-11α,9α-环氧甲撑前列腺素F2α）和ATP诱导的收缩以及乙酰胆碱诱导的舒张的调节作用。神经肽Y本身对动脉没有血管活性作用。在充血性心力衰竭大鼠中，内皮素-1的效力显著降低。神经肽Y和神经肽Y-(13-36)增强了充血性心力衰竭肠系膜动脉中内皮素-1诱导的收缩。在20%的充血性心力衰竭大鼠中，毒蜥毒素6c诱导了31±4%的收缩。神经肽Y还增强了充血性心力衰竭动脉中U46619和去甲肾上腺素诱导的收缩，但没有增强5-HT诱导的收缩。在假手术动物中，神经肽Y增强了去甲肾上腺素和5-HT诱导的收缩。这些增强作用被BIBP3226抑制。乙酰胆碱在两组中诱导了等效的舒张，且不受神经肽Y的影响。总之，充血性心力衰竭大鼠中神经肽Y的反应发生了改变。对血管活性物质的增强作用有所不同。涉及神经肽Y Y1和非神经肽Y1受体。
