OMEGA-CONOTOXIN GVIA AND PRAZOSIN, BUT NOT FELODIPINE, CAUSE POSTURAL HYPOTENSION IN RABBITS

1. The aim was to compare the effect of N-type calcium channel blockade by omega-conotoxin GVIA (omega-CTX) with alpha(1)-adrenoceptor or L-type calcium channel blockade on postural adaptation in conscious rabbits. 2. Orthostatic responses were assessed by rapidly tilting the rabbits through 90 degrees for 1 min. Tilts were performed before, 30 and 60 min after i.v. bolus administration of vehicle (propylene glycol 0.17 mL/kg; n = 8), prazosin (0.5 mg/kg; n = 8), felodipine (30 mu g/kg; n = 8) or omega-CTX (3 & 7 mu g/kg; n = 9). 3. Prazosin, felodipine or omega-CTX caused significant falls in mean arterial pressure (MAP) with corresponding increases in heart rate (HR). Vehicle administration had no effect on MAP but caused a small fall in HR. 4. Before drug or vehicle administration, a small rise in MAP and HR occurred in response to tilt in all rabbits. In the vehicle treatment group, similar responses were observed to tilt at 30 and 60 min, Postural hypotension was observed in the prazosin treatment group, but not following administration of felodipine. Tilts 30 and 60 min after omega-CTX (3 mu g/kg) caused an increase in HR but no change in MAP, different to the small presser response observed following vehicle administration. However, following administration of omega-CTX 7 mu g/kg (total dose, 10 mu g/kg), significant fans in MAP with tachycardia were observed in response to tilt. 5. In conclusion, orthostatic hypotension was observed following acute alpha(1)-adrenoceptor or N-type calcium channel blockade in the conscious rabbit. These findings are compatible with the expectation that agents which are directly sympatholytic interfere with postural adaptation. In contrast, L-type calcium channel antagonism with felodipine did not elicit postural hypotension.