Reynolds Patrick J, Fan Wei, Andresen Michael C
Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, Oregon 97239-3098, USA.
J Negat Results Biomed. 2006 May 18;5:6. doi: 10.1186/1477-5751-5-6.
Aortic baroreceptors (BRs) comprise a class of cranial afferents arising from major arteries closest to the heart whose axons form the aortic depressor nerve. BRs are mechanoreceptors that are largely devoted to cardiovascular autonomic reflexes. Such cranial afferents have either lightly myelinated (A-type) or non-myelinated (C-type) axons and share remarkable cellular similarities to spinal primary afferent neurons. Our goal was to test whether vanilloid receptor (TRPV1) agonists, capsaicin (CAP) and resiniferatoxin (RTX), altered the pressure-discharge properties of peripheral aortic BRs.
Periaxonal application of 1 microM CAP decreased the amplitude of the C-wave in the compound action potential conducting at <1 m/sec along the aortic depressor nerve. 10 microM CAP eliminated the C-wave while leaving intact the A-wave conducting in the A-delta range (<12 m/sec). These whole nerve results suggest that TRPV1 receptors are expressed along the axons of C- but not A-conducting BR axons. In an aortic arch--aortic nerve preparation, intralumenal perfusion with 1 microM CAP had no effect on the pressure-discharge relations of regularly discharging, single fiber BRs (A-type)--including the pressure threshold, sensitivity, frequency at threshold, or maximum discharge frequency (n = 8, p > 0.50) but completely inhibited discharge of an irregularly discharging BR (C-type). CAP at high concentrations (10-100 microM) depressed BR sensitivity in regularly discharging BRs, an effect attributed to non-specific actions. RTX (< or = 10 microM) did not affect the discharge properties of regularly discharging BRs (n = 7, p > 0.18). A CAP-sensitive BR had significantly lower discharge regularity expressed as the coefficient of variation than the CAP-resistant fibers (p < 0.002).
We conclude that functional TRPV1 channels are present in C-type but not A-type (A-delta) myelinated aortic arch BRs. CAP has nonspecific inhibitory actions that are unlikely to be related to TRV1 binding since such effects were absent with the highly specific TRPV1 agonist RTX. Thus, CAP must be used with caution at very high concentrations.
主动脉压力感受器(BRs)是一类起源于最靠近心脏的主要动脉的脑神经传入纤维,其轴突形成主动脉减压神经。BRs是机械感受器,主要参与心血管自主反射。这类脑神经传入纤维具有轻度髓鞘化的(A 型)或无髓鞘的(C 型)轴突,并且在细胞水平上与脊髓初级传入神经元有显著的相似性。我们的目标是测试香草酸受体(TRPV1)激动剂辣椒素(CAP)和树脂毒素(RTX)是否会改变外周主动脉BRs的压力-放电特性。
在轴突周围施加1微摩尔/升的CAP可降低沿主动脉减压神经以<1米/秒传导的复合动作电位中C波的幅度。10微摩尔/升的CAP消除了C波,而在Aδ范围(<12米/秒)传导的A波保持完整。这些全神经结果表明,TRPV1受体表达于C型而非A型传导的BR轴突上。在主动脉弓-主动脉神经标本中,管腔内灌注1微摩尔/升的CAP对规则放电的单纤维BRs(A 型)的压力-放电关系没有影响,包括压力阈值、敏感性、阈值频率或最大放电频率(n = 8,p > 0.50),但完全抑制了不规则放电的BR(C型)的放电。高浓度(10 - 100微摩尔/升)的CAP降低了规则放电的BRs的敏感性,这种作用归因于非特异性效应。RTX(≤10微摩尔/升)不影响规则放电的BRs的放电特性(n = 7,p > 0.18)。一个对CAP敏感的BR的放电规律性(以变异系数表示)显著低于对CAP耐药的纤维(p < 0.002)。
我们得出结论,功能性TRPV1通道存在于C型而非A 型(Aδ)有髓鞘的主动脉弓BRs中。CAP具有非特异性抑制作用,不太可能与TRV1结合有关,因为高特异性的TRPV1激动剂RTX不存在这种效应。因此,必须非常谨慎地使用高浓度的CAP。