Apparent vascular to cardiac sympatholytic selectivity of omega-conotoxin GVIA in the pithed rat.
The effects of omega-conotoxin GVIA (omega-CTX), a blocker of N-type voltage-operated calcium channels (VOCCs), were investigated in the pithed rat, omega-CTX (1.6 and 3.2 micrograms/kg i.v.) did not alter resting diastolic pressure or heart rate nor the pressor and chronotropic responses to noradrenaline injections (0.1-10 micrograms/kg). In contrast, the pressor responses to electrical stimulation of the whole spinal cord (0.2-6.4 Hz) were dose dependently reduced by omega-CTX whereas the concomitant tachycardia was less affected. When selective stimulation of the cardiac sympathetic outflow was applied, the resulting chronotropic response was more sensitive to omega-CTX. This result is discussed in the light of the possible interference of adrenal catecholamine release during whole spinal cord stimulation which is not sensitive to omega-CTX. These results provide in vivo evidence that omega-CTX is able to reduce sympathetic neurotransmission to the vasculature and the heart, presumably by blocking N-type VOCCs on pre- and post-ganglionic nerve terminals.
Baker Medical Research Institute, Prahran, Victoria, Australia.
D
D
Pruneau
J A
JA
Angus
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003655:Decerebrate State; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D013116:Spinal Cord / Q000502:physiology; D013565:Sympatholytics; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D010456:Peptides, Cyclic; D013565:Sympatholytics; D020866:omega-Conotoxin GVIA; D009638:Norepinephrine