Naphazoline-Induced Neuroendocrine Changes: Increases in ANP and cGMP Levels, but Suppression of NE, 3H-NE, and cAMP Levels in Rabbit Eyes

Abstract

The objective of this study was to determine whether naphazoline, an alpha 2 (α₂)/imidazoline (I₁) agonist, can alter endogenous levels of atrial natriuretic peptide (ANP) and norepinephrine (NE) in aqueous humor and cyclic nucleotide (cAMP, cGMP) accumulation and NE overflow inthe iris-ciliary body (ICB) of the rabbit eye. Topical naphazoline (25, 75, and 250 µg) caused a dose-dependent elevation of the ANP levels (36, 54, and 137 pg/ml, respectively) in aqueous humor. This effect was antagonized by pretreatment with efaroxan, an antagonist of I₁/α₂ receptors. Another α₂/I₁ agonist, moxonidine (75 µg topically), caused significant increases in ANP levels in aqueous humor, whereas other relatively selective α₂-adrenergic receptor agonists, brimonidine (50 µg topically) and oxymetazoline (75 µg topically), did not. In naphazoline (75 µg) pretreated eyes, the NE levels in aqueous humor were attenuated by 36% (from 6.0 to 3.8 pg/ml). Furthermore, naphazoline (1, 10, and 100 µmol/l) caused a dose-related inhibition of NE release from ICBs: 25, 45, and 80%, respectively. The isoproterenol (1 µmol/l) stimulated cAMP accumulation was inhibited 53% by naphazoline (100 µmol/l). In contrast, naphazoline significantly increased the cGMP levels in ICBs. These data demonstrate that naphazoline acts on I₁ receptors to increase ANP and to reduce NE levels in aqueous humor. The former effect could also contribute to elevation of cGMP levels and inhibition of cAMP accumulation in the ICB. Further studies will be required to determine if elevation of ANP levels is a critical component of naphazoline-induced alteration of aqueous humor dynamics.