Changes in vascular tone brought about by electrical field stimulation were studied in isolated guinea-pig and monkey pial arteries, using stimulus intensities similar to, or weaker than, those usually utilized by other investigators. In the guinea-pig, excitation of the smooth muscle cells was easily induced, even at low intensity stimulus parameters. This contraction faded upon repeated stimulation. Certain characteristics indicated that the response was neurogenic with excitation of perivascular sympathetic nerve terminals, despite the fact that it persisted after treatment with guanethidine and phentolamine and was only little reduced by tetrodotoxin; surgical sympathectomy or pretreatment with reserpine abolished the response, whereas removal of endothelium or mast cell degranulation was without effect. Attempts were made to further characterize the substance released. It was probably not noradrenaline, neuropeptide Y, adenosine triphosphate, serotonin, histamine or acetylcholine. In the monkey, similar low intensity stimulus parameters induced a fully tetrodotoxin-sensitive contractile response, attributable to the release of noradrenaline alone. By a minor increase in stimulus intensity, tetrodotoxin-resistant contractions, probably due to direct smooth muscle activation, could easily be obtained in pial arteries from both species. Tests were also performed to elucidate whether a dilatation, caused by a neurogenic transmitter release, could be obtained in these vessels. In both species, however, only a tetrodotoxin-resistant response was found, even at weak stimulus intensities, in agreement with previous observations in vessels from several other species. The present data illustrate the need for a careful choice of stimulus parameters when vascular tonic responses upon electrical field stimulation are used as an index for neurogenic release. They also demonstrate that such a response may, indeed, be neurogenic despite marked resistance to tetrodotoxin.
|Journal||Archives internationales de pharmacodynamie et de therapie|
|Publication status||Published - 1989|
Subject classification (UKÄ)
- Pharmacology and Toxicology