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

1. The aim was to compare the effect of N-type calcium channel blockad e by omega-conotoxin GVIA (omega-CTX) with alpha(1)-adrenoceptor or L- type calcium channel blockade on postural adaptation in conscious rabb its. 2. Orthostatic responses were assessed by rapidly tilting the rab bits 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 administratio n had no effect on MAP but caused a small fall in HR. 4. Before drug o r vehicle administration, a small rise in MAP and HR occurred in respo nse to tilt in all rabbits. In the vehicle treatment group, similar re sponses were observed to tilt at 30 and 60 min, Postural hypotension w as observed in the prazosin treatment group, but not following adminis tration 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/k g), significant fans in MAP with tachycardia were observed in response to tilt. 5. In conclusion, orthostatic hypotension was observed follo wing acute alpha(1)-adrenoceptor or N-type calcium channel blockade in the conscious rabbit. These findings are compatible with the expectat ion that agents which are directly sympatholytic interfere with postur al adaptation. In contrast, L-type calcium channel antagonism with fel odipine did not elicit postural hypotension.