Contrasting actions of cocaine, local anaesthetic and tetrodotoxin on discharge properties of rat aortic baroreceptors.
1. Effects of cocaine, lignocaine, benzocaine and tetrodotoxin (TTX) on the simultaneously measured pressure- and diameter-discharge frequency relations of single fibre baroreceptors were compared in rat in vitro aortic arch-aortic nerve preparations. 2. Between 1 and 10 microM, cocaine produced selective increases in the pressure threshold shifting the pressure-response curve without altering the gain or threshold frequency. At near-blocking concentrations, gain was depressed as well. Cocaine experiments were done in nitroprusside (NP, 1 microM). Neither NP or NP with cocaine altered diameter (P > 0.36). 3. Lignocaine (at > 10 microM) and benzocaine (at > 100 microM) shifted pressure-response curves to higher pressures and generally depressed discharge by increasing pressure threshold and decreasing maximum discharge frequency (P < 0.05). Gain decreased and threshold frequency increased at higher concentrations. Diameter was unaffected by lignocaine or benzocaine (P > 0.14). 4. TTX increased thresholds and discharge frequencies at threshold but did not shift pressure-discharge curve locations. This produced superimposable discharge curves with changes occurring as losses of discharge points in the threshold region. Diameter was unaffected by TTX (P > 0.80). 5. The contrasting patterns of effects between TTX and local anaesthetics suggest that blockade of TTX-sensitive sodium channels alone may not be responsible for the effects of cocaine, lignocaine and benzocaine.
Andresen
M C
MC
Department of Physiology, Oregon Health Sciences University, Portland 97201-3098.
Brodwick
M
M
Yang
M
M
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000294:innervation*; D001566:Benzocaine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*
D000779:Anesthetics, Local; D015222:Sodium Channels; D013779:Tetrodotoxin; D008012:Lidocaine; D003042:Cocaine; D001566:Benzocaine