Effects of B-HT 920 in the eye and on regional blood flows in anaesthetized and conscious rabbits

Abstract

The influence of unilateral ocular instillation of B-HT 920 (50 µg) on regional ocular, cerebral and peripheral blood flows was investigated with the labelled microsphere method in conscious and anaesthetized albino rabbits. In urethane-anaesthetized rabbits the intraocular pressure (IOP) fell during 1 hr following topical B-HT 920 whereas no changes in regional blood flows were observed. Only in conscious rabbits was a decrease in regional blood flows found. B-HT 920 caused a short-term reduction in choroidal blood flow by about 20%. Transient vasoconstrictor effects, due to systemic absorption, were also seen in some extraocular tissues. Concomitantly, B-HT 920 reduced the total cerebral blood flow (CBF) by 23%. In the grey matter and hypothalamic region the decrease in flow was about 20%, while in the hippocampal region, thalamic region, collides and pons-mesencephalon it was about 10%. In experiments with direct blood flow determination from an opened vortex vein, there was no consistent change of uveal vascular resistance, while IOP and mean arterial pressure (MAP) fell dose-dependently following cumulative intravenously administered bolus doses (10 and 50 µg/kg) of B-HT 920. Unilateral loss of the mediated sympathetic tone seemed to increase the ocular responses to B-HT 920, unmasking a vasoconstrictor effect. Additional systemic pretreatment with the selective blocking agents rauwolscine and sulpiride suggests that B-HT 920 produces its ocular hypotensive effect, predominantly by acting on dopamine (DA₂) receptors in the eye rather than on α₂ -adrenoceptors, and its ocular vasoconstrictor effects via both receptor types.