迷走神经释放血管活性肠肽可促进离体的有神经支配的大鼠心脏出现迷走神经性心动过速。

Vagal release of vasoactive intestinal peptide can promote vagotonic tachycardia in the isolated innervated rat heart.

作者信息

Shvilkin A, Danilo P, Chevalier P, Chang F, Cohen I S, Rosen M R

机构信息

Department of Pharmacology, Columbia University, New York, NY 10032.

出版信息

Cardiovasc Res. 1994 Dec;28(12):1769-73. doi: 10.1093/cvr/28.12.1769.

DOI:10.1093/cvr/28.12.1769

PMID:7867028

Abstract

OBJECTIVE

The aim was to determine the extent to which endogenous release of vasoactive intestinal polypeptide (VIP) might be implicated in the modulation of sinoatrial rate in the presence and absence of muscarinic blockade or beta blockade.

METHODS

Langendorff perfused rat hearts were studied with the right vagus intact. The hearts were maintained in sinus rhythm and subjected to right vagal stimuli of 5, 10, 20, and 30 Hz.

RESULTS

Administration of exogenous VIP, 10(-8) M, increased sinus rate by 20% (p < 0.05). This increase in heart rate was reduced significantly to 8% by the VIP antagonist [D-p-Cl-Phe6, Leu17]VIP, 10(-7) M, which alone had no effect on sinus rate. Vagal stimulation reduced sinus rate from a control of 254(SEM 2) to 164(17) beats.min-1 (p < 0.05) at 20 Hz. VIP, 10(-8) M, increased these rates to 284(6) and 220(21) beats.min-1 (p < 0.05). In another eight vagally stimulated hearts, frequencies of 5-20 Hz reduced sinus rate. At 30 Hz heart rate increased in five, and the resultant rate was significantly faster in these [154(10) beats.min-1] than in the remainder [98(12) beats.min-1, p < 0.05]. Vagal stimulation also increased sinus rate (p < 0.05) in four of seven additional hearts perfused with atropine, 2 x 10(-6) M. This increase was completely abolished by [D-p-Cl-Phe6, Leu17]VIP. That the effect was not beta adrenergic was demonstrated in eight experiments using atropine plus propranolol, 1 x 10(-7) M. A vagally induced increment in rate still occurred (p < 0.05) and was abolished by [D-p-CL-Phe6, Leu17]VIP. The ability to ascribe a rate change to VIP release was maximal in the presence of propranolol and atropine, intermediate in the presence of atropine alone, and minimal in the absence of muscarinic or beta blockade.

CONCLUSIONS

Vagally released VIP is capable of limiting the decrement in sinus rate that occurs at high frequencies of vagal stimulation, and in some circumstances can actually increment sinus rate. Its role as an endogenous modulator of vagal effects on heart rate and as a possible cause of vagal and postvagal tachycardias should be further explored.

摘要

目的

本研究旨在确定在存在和不存在毒蕈碱阻断或β阻断的情况下，血管活性肠肽（VIP）的内源性释放可能在多大程度上参与窦房结速率的调节。

方法

在保留右迷走神经完整的情况下，对经Langendorff灌注的大鼠心脏进行研究。使心脏维持窦性心律，并施加5、10、20和30Hz的右迷走神经刺激。

结果

给予10⁻⁸M的外源性VIP可使窦性速率增加20%（p<0.05）。10⁻⁷M的VIP拮抗剂[D-p-Cl-Phe⁶，Leu¹⁷]VIP可将这种心率增加显著降低至8%，该拮抗剂单独使用时对窦性速率无影响。迷走神经刺激可使窦性速率从254（标准误2）次/分钟的对照值在20Hz时降至164（17）次/分钟（p<0.05）。10⁻⁸M的VIP可将这些速率分别提高至284（6）和220（21）次/分钟（p<0.05）。在另外8个接受迷走神经刺激的心脏中，5-20Hz的频率降低了窦性速率。在30Hz时，5个心脏的心率增加，这些心脏的最终速率[154（10）次/分钟]显著快于其余心脏[98（12）次/分钟，p<0.05]。在另外7个用2×10⁻⁶M阿托品灌注的心脏中，迷走神经刺激也增加了窦性速率（p<0.05）。这种增加被[D-p-Cl-Phe⁶，Leu¹⁷]VIP完全消除。在8个使用阿托品加1×10⁻⁷M普萘洛尔的实验中证明该效应不是β肾上腺素能的。迷走神经诱导的速率增加仍然发生（p<0.05），并被[D-p-Cl-Phe⁶，Leu¹⁷]VIP消除。在存在普萘洛尔和阿托品的情况下，将速率变化归因于VIP释放的能力最大，在仅存在阿托品的情况下居中，而在不存在毒蕈碱或β阻断的情况下最小。