Mechanisms of the cutaneous vasodilator response to local external pressure application in rats: involvement of CGRP, neurokinins, prostaglandins and NO.
作者信息
Fromy B, Merzeau S, Abraham P, Saumet J L
机构信息
Laboratoire de Physiologie, Faculté de Médecine d'Angers, F-49045 Angers, cedex France.
Local pressure-induced vasodilation (PIV) is a neural vasodilator response to non-nociceptive externally applied pressure in the skin, previously described in humans. We first determined whether PIV exists in rats and depends on capsaicin-sensitive fibres as it does in humans. We then examined the mediators involved in the efferent pathway of PIV. 2. Cutaneous blood flow was measured by laser Doppler flowmetry during 11.1 Pa s(-1) increases in local applied pressure in anaesthetized rats. The involvement of capsaicin-sensitive fibres in PIV was tested in rats treated neonatally with capsaicin. To antagonize CGRP, neurokinin-1, -2, or -3 receptors, different groups of rats were treated with CGRP(8 - 37), SR140333, SR48968 or SR142801, respectively. Prostaglandins involvement was tested with indomethacin treatment. To inhibit nitric oxide synthase (NOS) activity or specific neuronal NOS, rats were treated with N(G)-nitro-L-arginine or 7-nitroindazole, respectively. 3. PIV was found in rats, as in humans. PIV was abolished by neonatal treatment with capsaicin and by administration of CGRP(8 - 37) but remained unchanged with SR140333, SR48968 and SR142801 treatments. Prostaglandin inhibition resulted in a significant decrease in PIV. Inhibition of NOS abolished PIV, whereas inhibition of neuronal NOS caused a diminution of PIV. 4. These data suggest that PIV depends on capsaicin-sensitive fibres in rats, as in humans. It appears that CGRP plays a major role in the PIV, whereas neurokinins have no role. Furthermore, PIV involves a contribution from prostaglandins and depends on endothelial NO, whereas neuronal NO has a smaller role.
摘要
局部压力诱导的血管舒张（PIV）是皮肤对非伤害性外部施加压力的一种神经性血管舒张反应，此前已在人类中有所描述。我们首先确定大鼠中是否存在PIV，以及它是否像在人类中一样依赖辣椒素敏感纤维。然后我们研究了参与PIV传出通路的介质。2. 在麻醉大鼠局部施加压力以11.1 Pa s(-1)的速率增加期间，通过激光多普勒血流仪测量皮肤血流量。在用辣椒素进行新生期处理的大鼠中测试辣椒素敏感纤维在PIV中的作用。为了拮抗降钙素基因相关肽（CGRP）、神经激肽-1、-2或-3受体，分别用CGRP(8 - 37)、SR140333、SR48968或SR142801处理不同组的大鼠。用吲哚美辛处理测试前列腺素的作用。为了抑制一氧化氮合酶（NOS）活性或特异性神经元型NOS，分别用N(G)-硝基-L-精氨酸或7-硝基吲唑处理大鼠。3. 正如在人类中一样，在大鼠中也发现了PIV。新生期用辣椒素处理以及给予CGRP(8 - 37)可消除PIV，但用SR140333、SR48968和SR142801处理时PIV保持不变。抑制前列腺素会导致PIV显著降低。抑制NOS可消除PIV，而抑制神经元型NOS会使PIV减小。4. 这些数据表明，与人类一样，大鼠中的PIV依赖于辣椒素敏感纤维。似乎CGRP在PIV中起主要作用，而神经激肽不起作用。此外，PIV涉及前列腺素的作用且依赖于内皮型一氧化氮，而神经元型一氧化氮的作用较小。
