Roossien A, Brunsting J R, Nijmeijer A, Zaagsma J, Zijlstra W G
Department of Medical Physiology, University of Groningen, Netherlands.
Cardiovasc Res. 1997 Feb;33(2):392-9. doi: 10.1016/s0008-6363(96)00202-7.
The vagal cardiac accelerator (VCA) system takes part in the nervous control of the heart rate. In the present study we tried to adduce evidence that vasoactive intestinal polypeptide (VIP) contributes to vagally induced cardioaccelerations.
The effect of VIP on heart rate and arterial blood pressure was investigated after unmasking the inherent VCA activity by blocking the sympathetic accelerator and vagal decelerator influences on heart rate in conscious dogs.
Following intravenous administration of VIP (10 micrograms i.v.) the heart rate increased by 43.6 +/- 6.7 (28.1 +/- 4.7%), from 165.6 +/- 8.5 to 209.1 +/- 7.0 beats/min (P < 0.001) and the mean arterial blood pressure decreased by 47.5 +/- 3.2 (37.9 +/- 3.0%), from 126.6 +/- 2.6 to 79.1 +/- 4.9 mmHg (P < 0.001) (n = 11). After VCA activity was reflexly enhanced by alpha 1-adrenoceptor stimulation with methoxamine, VIP increased heart rate by 36.9 +/- 7.3 (21.5 +/- 4.6%), from 179.8 +/- 5.2 to 216.7 +/- 5.8 beats/min (P < 0.001) and decreased mean arterial pressure by 79.1 +/- 6.4 (46.7 +/- 3.5%), from 168.2 +/- 4.1 to 89.1 +/- 5.0 mmHg (P < 0.001). Hence, the VIP-induced tachycardia, expressed in relative values, shows a significant attenuation after the administration of methoxamine (P < 0.05). The increase in heart rate induced by VIP appeared to be inversely related to the prevailing VCA activity, both before (r = -0.744, P = 0.009) and after methoxamine (r = -0.689, P = 0.019). The VIP-induced tachycardia is certainly not reflexly induced by the fall in arterial pressure, because intracoronary administration of VIP (0.5 microgram i.c.) caused an appreciable increase in the heart rate by 63.7 +/- 13.0 (46.4 +/- 10.4%), from 143.0 +/- 8.1 to 208.7 +/- 12.0 beats/min (P < 0.005), whereas the mean arterial pressure only slightly changed (-7.7 +/- 2.0 mmHg) (P < 0.05) (n = 6). In addition, VIP (10 micrograms i.v.) also caused a tachycardia in vagotomized dogs with blocked beta-adrenergic and muscarinic receptors. The administration of the VIP antagonists [D-p-CI-Phe6, Leu17]-VIP (50-150 micrograms i.c.) and [Lys1, Pro2,5, Leu17]-VIP (20 micrograms i.c.) did not result in alterations in VCA activity nor did the VIP antagonists block the VCA reflex response to a rise in arterial pressure. However, none of the VIP antagonists reduced the VIP-induced tachycardia either.
Vasoactive intestinal polypeptide is likely to play a part in the vagal cardiac accelerator system. However, conclusive evidence for its role as the terminal transmitter in the VCA pathway will have to wait for the availability of a specific cardiac VIP receptor antagonist.
迷走神经心脏加速（VCA）系统参与心率的神经控制。在本研究中，我们试图提供证据表明血管活性肠肽（VIP）有助于迷走神经诱导的心脏加速。
通过阻断清醒犬交感神经加速器和迷走神经减速对心率的影响来揭示内在VCA活性后，研究VIP对心率和动脉血压的影响。
静脉注射VIP（10微克）后，心率从165.6±8.5次/分钟增加到209.1±7.0次/分钟，增加了43.6±6.7（28.1±4.7%）（P<0.001），平均动脉血压从126.6±2.6毫米汞柱降至79.1±4.9毫米汞柱，降低了47.5±3.2（37.9±3.0%）（P<0.001）（n = 11）。用甲氧明刺激α1-肾上腺素能受体使VCA活性反射性增强后，VIP使心率从179.8±5.2次/分钟增加到216.7±5.8次/分钟，增加了36.9±7.3（21.5±4.6%）（P<0.001），平均动脉血压从168.2±4.1毫米汞柱降至89.1±5.0毫米汞柱，降低了79.1±6.4（46.7±3.5%）（P<0.001）。因此，以相对值表示的VIP诱导的心动过速在给予甲氧明后显示出显著减弱（P<0.05）。VIP诱导的心率增加似乎与主要的VCA活性呈负相关，无论是在给予甲氧明之前（r = -0.744，P = 0.009）还是之后（r = -0.689，P = 0.019）。VIP诱导的心动过速肯定不是由动脉压下降反射性诱导的，因为冠状动脉内注射VIP（0.5微克）使心率明显增加了63.7±13.0（46.4±10.4%），从143.0±8.1次/分钟增加到208.7±12.0次/分钟（P<0.005），而平均动脉血压仅略有变化（-7.7±2.0毫米汞柱）（P<0.05）（n = 6）。此外，VIP（10微克静脉注射）在β-肾上腺素能和毒蕈碱受体阻断的迷走神经切断犬中也引起心动过速。给予VIP拮抗剂[D-p-CI-Phe6，Leu17]-VIP（50 - 150微克冠状动脉内注射）和[Lys1，Pro2,5，Leu17]-VIP（20微克冠状动脉内注射）既未导致VCA活性改变，也未阻断VCA对动脉压升高的反射反应。然而，VIP拮抗剂也均未降低VIP诱导的心动过速。
血管活性肠肽可能在迷走神经心脏加速系统中起作用。然而，关于其作为VCA途径中终末递质作用的确凿证据，还需等待特异性心脏VIP受体拮抗剂的出现。
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