Pintér A, Nadeau R, Dandan N, Pagé P L
Research Centre, Hôpital du Sacré-Coeur de Montréal, Canada.
Can J Physiol Pharmacol. 1998 Apr;76(4):457-62. doi: 10.1139/cjpp-76-4-457.
Vasoactive intestinal polypeptide (VIP) was either injected intravenously (300 pmol.kg-1) or perfused (1 nmol in 1 min) into the sinus node artery (SNA) in anesthetized dogs to study its effect on subsidiary atrial pacemakers. Isochronal maps were obtained from 128 unipolar electrograms recorded on the epicardial surface of both atria in nine animals. When VIP was perfused into the SNA or injected intravenously, heart rate increased by 29 +/- 16% and 12 +/- 12%, and blood pressure decreased by 16 +/- 15 mmHg (1 mmHg = 133.3 Pa) and 24 +/- 18 mmHg, respectively. No significant change in heart rate (3 +/- 6% decrease) accompanied a similar decrease in blood pressure after an intravenous sodium nitroprusside perfusion. The perfusion of VIP into the SNA as well as the intravenous injection of VIP induced a shift of the pacemaker site to the region of Bachmann's bundle in a third of the preparations, while the pacemaker remained in the sinus node area in two thirds. A perfusion of isoproterenol into the SNA produced a similar heart rate increase (32 +/- 14%, NS vs. VIP), and shifted the pacemaker site rostrally within the sinus node in three of five preparations, or to the region of Bachmann's bundle in two of five preparations. The response to VIP in the location of the pacemaker was significantly different from the response to isoproterenol. Repeated perfusions of VIP into the SNA after 10-, 25-, 40-, and 60-min intervals produced 2 +/- 13% (p < 0.005 vs. the effect of first VIP administration), 14 +/- 12% (p < 0.05), 10 +/- 12% (p < 0.05) and 30 +/- 13% (NS) heart rate increases, respectively, thereby demonstrating a tachyphylactic effect. In conclusion, VIP seems to exert its positive chronotropic effect directly (probably via specific VIP receptors), although the phenomenon of tachyphylaxis may suggest an indirect sympathomimetic mechanisms.
在麻醉犬中，将血管活性肠肽（VIP）静脉注射（300 pmol·kg-1）或灌注到窦房结动脉（SNA）中（1分钟内1 nmol），以研究其对心房次级起搏点的影响。从9只动物心房心外膜表面记录的128个单极电图获得等时图。当将VIP灌注到SNA或静脉注射时，心率分别增加29±16%和12±12%，血压分别降低16±15 mmHg（1 mmHg = 133.3 Pa）和24±18 mmHg。静脉注射硝普钠后，血压有类似下降，但心率无显著变化（下降3±6%）。将VIP灌注到SNA以及静脉注射VIP，在三分之一的标本中可使起搏点部位移至巴赫曼束区域，而在三分之二的标本中起搏点仍位于窦房结区域。将异丙肾上腺素灌注到SNA中可使心率有类似增加（32±14%，与VIP相比无显著差异），在五分之三的标本中使起搏点部位在窦房结内向前移位，在五分之二的标本中移至巴赫曼束区域。起搏点位置对VIP的反应与对异丙肾上腺素的反应显著不同。在间隔10、25、40和60分钟后重复将VIP灌注到SNA中，心率分别增加2±13%（与首次给予VIP的效果相比，p < 0.005）、14±12%（p < 0.05）、10±12%（p < 0.05）和30±13%（无显著差异），从而显示出快速耐受性效应。总之，VIP似乎直接发挥其正性变时作用（可能通过特定的VIP受体），尽管快速耐受性现象可能提示存在间接拟交感神经机制。
