Abstract

Evidence suggests that in some species (cats, rabbits, and possibly humans) α-adrenoceptors in the iris dilator muscle are “atypical” in that they cannot be readily classified by conventional criteria. This study was undertaken in an attempt to characterize the α-adrenoceptor subtype(s) mediating sympathetically elicited mydriasis in rats. Frequency-response pupillary dilator curves were generated by stimulation of the preganglionic cervical sympathetic nerve (1–32 Hz) in pentobarbital-anesthetized rats. Evoked responses were inhibited by systemic administration of nonselective α-adrenergic antagonists, phentolamine (0.3–10 mg/kg) and phenoxybenzamine (0.03–1 mg/kg). The selective α₁-adrenergic antagonist, prazosin (0.01–1 mg/kg), also was effective, although α₂-adrenergic antagonism with rauwolscine (0.1–1 mg/kg) was not. α_1A-Adrenoceptor-selective antagonists, 2-([2,6-dimethoxyphenoxyethyl]aminomethyl)-1,4-benzodioxane (WB-4101; 0.1–1 mg/kg) and 5-methylurapidil (0.1–1 mg/kg), as well as the α_1D-adrenoceptor-selective antagonist 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY-7378; 1–3 mg/kg), were used to determine the subtype(s) involved. Evoked mydriasis was significantly antagonized by both WB-4101 and 5-methylurapidil but not by BMY-7378. These results suggest that, unlike some other species, adrenoceptors in the rat iris dilator mediating neurogenic mydriasis are “typical” and, in addition, can be characterized as being primarily of the α_1A-adrenoceptor subtype.