The ability of ruthenium red to reduce the autonomic reflexes and peptide release evoked by capsaicin administration in the pig in vivo.
In the present study we have investigated the cardiovascular effects and peptide-releasing actions of different capsaicin doses in the absence and presence of the inhibitor of Ca2+ fluxes, ruthenium red, in the pig in vivo. Bolus injections of capsaicin (10, 100 and 1000 micrograms kg-1 i.v.) evoked a concentration-dependent increase in mean arterial pressure and heart rate (HR), while in the bronchial and nasal circulations, a fall in vascular resistance was observed. At the highest capsaicin dose used, there was, in addition, a marked increase in arterial levels of calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (LI). Ruthenium red (RR) significantly reduced the CGRP-LI release, but not the outflow of NPY-LI, at the highest dose of capsaicin as well as the functional effects evoked by low dose capsaicin administration. The inhibitory effects of RR were reversible, i.e. 30 min after ruthenium red administration, bolus injections of capsaicin (10 and 100 micrograms kg-1) induced responses similar to those seen in controls. It is concluded that capsaicin given intravenously to the pig produces profound haemodynamic effects and release of CGRP- and NPY-LI through direct activation of a population of C-fibre endings and increased autonomic discharge. RR inhibits not only the local peptide-releasing properties of capsaicin, but also the centrally directed discharge activity leading to reflex responses, with the latter being less sensitive to RR.
Alving
K
K
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Franco-Cereceda
A
A
D000758:Anesthesia; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D001980:Bronchi / Q000098:blood supply; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D009297:Nasal Mucosa / Q000098:blood supply; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D012430:Ruthenium Red / Q000494:pharmacology*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D009478:Neuropeptide Y; D009479:Neuropeptides; D012430:Ruthenium Red; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D001920:Bradykinin