Relaxation effects of diltiazem, verapamil, and tolazoline on isolated cat ophthalmociliary artery.
This study investigates the ability of an alpha 1-adrenergic blocker, tolazoline, two Ca2+ entry channel blockers, verapamil and diltiazem, acetylcholine and Ca(2+)-free solutions to relax alpha 1-adrenergically activated cat ophthalmociliary artery ring segments. The form of a contraction elicited with adrenaline, noradrenaline or phenylephrine was shown to depend on the passive tension set. As passive tension was increased, which is equivalent to increasing blood pressure in vivo, the alpha 1-adrenergic elicited contraction became more sustained. Incubation with the Ca2+ channel blockers diltiazem and verapamil was ineffective in reducing the phasic response to the alpha 1-adrenergic agonists whereas addition of these blockers in increasing concentrations during a sustained adrenergic contraction caused a graded and significant relaxation. This implies that therapeutic use of Ca2+ channel blockers may act directly on the ophthalmociliary artery to inhibit the autonomic control of sustained tone in this vessel. Removal of exogenous Ca2+ from the bathing medium initially reduced the phasic component and eliminated the tonic component of the alpha 1-adrenergic contraction. Repeated exposure of the ring segment to Ca(2+)-free medium further reduced the phasic component elicited with alpha 1-adrenergic contraction. Pre-incubation with the alpha 1-adrenergic blocker Tolazoline reduced the alpha 1-adrenergic antagonist phasic response only at high concentrations (10(-4) M), whereas Tolazoline applied during the tonic phase was an effective relaxant at lower concentrations. Acetylcholine added to the bath during an alpha 1-adrenergic contraction induced relaxation at low concentrations and contraction for higher concentrations. The relaxation was eliminated by removal of the endothelial cell layer. These data support the notion that the phasic component of an alpha 1-adrenergic contraction is mainly dependent on intracellular Ca2+ stores whereas the tonic component relies almost exclusively on extracellular Ca2+. It is suggested that Ca2+ channel blockers and alpha 1-adrenergic antagonists may potentially play a role in relaxing the ophthalmociliary artery to improve the ocular circulation in vascular diseases in which there is considerable vascular tone present.