EVIDENCE FOR A NEW ROLE OF NATRIURETIC PEPTIDES - CONTROL OF INTRAOCULAR-PRESSURE

To study the possible physiological role of atrial natriuretic peptide (ANP) in the regulation of intraocular pressure (IOP) the effects of an increase of endogenous ANP within the physiological range induced b y the neutral endopeptidase 24.11 (NEP) inhibitor candoxatril were exa mined. In a single masked placebo controlled trial, seven patients wer e studied with normal IOP (six male, one female; average age 50 (range 37-62 years). Intraocular pressure in each eye was measured after 2 w eeks of placebo, after 4 weeks of candoxatril 200 mg twice daily, and during the first 3 days of placebo washout. With 4 weeks of candoxatri l, endogenous plasma ANP levels increased from 4.2 (SEM 1.5) to 6.0 (1 .5) pmol/l (p<0.04) and there was a significant decrease in mean arter ial pressure from 119 (4) to 110 (3) mm Hg (p<0.02; 12 hours after tre atment). There was a significant reduction in IOP after 4 weeks' treat ment with candoxatril (right eye 2.1 (0.8) mm Hg, p<0.05 paired t test , left eye 2.8 (0.8) mm Hg, p<0.02). The mean fall in IOP was 11% (4%) in the right eye and 16% (3%) in the left eye and the fall in IOP was greater the higher the initial IOP. The reduction in IOP with chronic NEP inhibition was positively correlated with the increase in ANP lev els but not with changes in blood pressure. These findings suggest tha t ANP may play a physiological role in the regulation of IOP. As the f all in IOP was greater in subjects with higher initial IOP, NEP inhibi tors may be of therapeutic value in the management of glaucoma.