[The effect of endothelin and protein kinase C on the vasoactive mechanisms of beta A(4)25-35 at skin microvasculature].
OBJECTIVE
The aim of the present study is to investigate the mechanisms of beta A(4)25-35 at the level of skin microvascula ture.


METHODS
Using a blister model in rat skin, we examined the possibilities that beta A(4)25-35 induces VC effect via the release of endothelin and the involvement of protein kinase C (PKC). Changes in microvascular blood flow were monitored using laser Doppler flowmetry and the area within the response curve measured.


RESULTS
The results showed that either the endothelin receptor antagonist (BQ--123 at 10 mumol) or PKC inhibitor (bisindolylmaleimide at 1 mu mol) was perfused before beta A(4)25-35. It prevented beta A(4)25-35 from inducing a VC effect and allowed a subsequent SP to induce a normal response.


CONCLUSIONS
Both endothelin and PKC play a role in the mechanism be which beta A(4)25-35 induces VC effect and modulates subsequent SP response at the level of skin microvasculature. We suggest the possibility that the vascular activity of beta A(4)25-35 could be mediated via endothelin with subsequent activation of PKC.
Department of Neurology, Beijing Hospital.
H
H
Chen
Z
Z
Khalil
R D
RD
Helme
D000544:Alzheimer Disease / Q000209:etiology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D008833:Microcirculation; D010456:Peptides, Cyclic / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply*; D013373:Substance P / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D008301:Maleimides; D010456:Peptides, Cyclic; D013373:Substance P; D011493:Protein Kinase C; C088060:bisindolylmaleimide; C072247:cyclo(Trp-Asp-Pro-Val-Leu)