Selective alpha 1A-adrenoceptor stimulation induces Mueller's smooth muscle contraction in an isolated canine upper eyelid preparation.

PURPOSE

It has been demonstrated that in patients with aponeurotic blepharoptosis, alpha(1)-adrenoceptor stimulation causes the contraction of the upper eyelid tarsal smooth muscle (Mueller's muscle) and opening of the eye. However, alpha(1)-adrenoceptor subtypes mediating the contraction of Mueller's muscle are still unclear. This study was designed to identify the alpha(1)-adrenoceptor subtypes in Mueller's muscle.

MATERIALS AND METHODS

A newly developed canine upper eyelid preparation was retrogradely perfused with a drug-containing Krebs-Henseleit solution through the angular vein in a temperature-controlled organ chamber. The contraction of the preparation was measured with a force-displacement transducer.

RESULTS

Phenylephrine, an alpha(1)-adrenoceptor agonist, increased the upper eyelid contractile force in a dose-dependent manner (K(0.5) = 110 nmol). Interestingly, the contraction in response to phenylephrine was persistent and hardly recovered to a base line level for more than 100 min after washout of the drug. WB4101 (100 nM), an alpha(1A)- and alpha(1D)-adrenoceptor antagonist, but not BMY7378 (100 nM), a selective alpha(1D)-adrenoceptor antagonist, competitively inhibited the phenylephrine-induced contraction. ABT-866, a selective alpha(1A)-adrenoceptor agonist, increased the upper eyelid contractile force as effectively as phenylephrine in a dose-dependent manner (K(0.5) = 190 nmol), and the contraction continued again for more than 100 min.

CONCLUSION

These results suggest that selective alpha(1A)-adrenoceptor agonists, such as ABT-866, induce the sustained Mueller's muscle contraction and may be useful in pharmacological treatment of blepharoptosis.