Apparent vascular to cardiac sympatholytic selectivity of ω-conotoxin GVIA in the pithed rat

Abstract

The effects of ω-conotoxin GVIA (ω-CTX), a blocker of N-type voltage-operated calcium channels (VOCCs), were investigated in the pithed rat. ω-CTX (1.6 and 3.2 μg/kg i.v.) did not alter resting diastolic pressure or heart rate nor the pressor and chronotropic responses to noradrenaline injections (0.1–10 μg/kg). In contrast, the pressor responses to electrical stimulation of the whole spinal cord (0.2–6.4 Hz) were dose dependently reduced by ω-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 ω-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 ω-CTX. These results provide in vivo evidence that ω-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.