OMEGA-CONOTOXIN GVIA, THE N-TYPE CALCIUM-CHANNEL INHIBITOR, IS SYMPATHOLYTIC BUT NOT VAGOLYTIC - CONSEQUENCES FOR HEMODYNAMICS AND AUTONOMIC REFLEXES IN CONSCIOUS RABBITS

We investigated the effects of the N-type calcium channel blocking agent, ω-conotoxin GVIA, on the resting hemodynamics and on some autonomic reflexes in the conscious rabbit. ω-Conotoxin 3 and 10 μg/kg i.v. reduced mean arterial blood pressure by 16 ± 2 and 25 ± 3 mm Hg, respectively, over 30 min accompanied by a tachycardia. Renal vascular conductance (Doppler flow-meter) increased by 27.6 ± 3.7 and 38.6 ± 10.3% at 30 min after ω-conotoxin 3 and 10 μg/kg, respectively. Vasodilatation was also observed but to a lesser extent in the hindquarter and mesenteric vascular beds. The baroreceptor-heart rate reflex was evoked by a drug method (bolus injection of sodium nitroprusside and phenylephrine) and by inflation of perivascular balloons implanted on the thoracic vena cava and aorta. ω-Conotoxin (3 μg/kg) abolished the sympathetic component of the cardiac baroreceptor reflex without affecting vagal efferent activity. In addition, marked vagal-mediated bradycardia from (a) the "Bezold-Jarisch-like" reflex evoked by serotonin (1-10 ωUg/kg i.v.) and (b) the nasopharyngeal reflex evoked by cigarette smoke were unaffected by ω-conotoxin (3-10 μg/kg). We conclude that ω-conotoxin-induced N-type calcium channel blockade abolishes sympathetic but not vagal cardiac efferent activity. The hypotension and peripheral vasodilatation are probably due to the prejunctional sympatholytic action of the peptide. These N-type calcium channels are thus limited to the sympathetic varicosities in the rabbit. © 1990 Raven Press, Ltd., New York.