TIMOLOL DECREASES AQUEOUS-HUMOR FLOW BUT NOT NA+ MOVEMENT FROM PLASMATO AQUEOUS

Purpose. To determine whether the well-known effect of timolol in redu cing ocular pressure and aqueous humor (AH) flow is a function of redu ced Na+ movement from plasma to aqueous. Previously, the authors have shown this to be the case for carbonic anhydrase inhibitors. Methods. The rate of appearance of Na-22 in rabbit posterior aqueous was measur ed 1 to 3 minutes after the intravenous injection (time T) of the isot ope. One hour before this, the animals received one of the following: two drops of 0.5% timolol, two drops of 3.5% pilocarpine, or 25 mg/kg intravenous methazolamide. At 1 minute (T + 1), a posterior chamber sa mple was taken; 2 minutes later (T + 3) a second sample was removed fr om the fellow eve. The rate constant of sodium accession is simply the difference between the two counts/2 minutes. Aqueous flow was measure d by dilution of sulfacetamide marker as described preciously. Results . The rate constant (k(in)) for sodium entering the posterior chamber was 0.036 +/- 0.004 minute(-1) (n = 17). Corresponding to previous fin dings, methazolamide (25 mg/kg intravenous) reduced this to 0.023 +/- 0.003 minute(-1) (n = 14). Conversely, timolol (two drops of 0.5% solu tion) had no effect on k(in), which measured 0.037 +/- 0.004 minute(-1 ) (n = 12). Similarly, as expected, pilocarpine had no effect on k(in) (0.035 +/- 0.003 minute(-1)). Control flow was 3.9 mu l/minute +/- 0. 4; after timolol, 2.5 mu l/minute +/- 0.1; after methazolamide, 2.4 mu l/minute +/-: 0.2; after pilocarpine, 3.6 mu l/minute +/- 0.2. These are converted to rate constants by dividing by volume of posterior aqu eous (60 mu l). The control rate constant for fluid entry was 0.065 mi nute(-1), 1.8-fold higher than for sodium. Conclusions. A central dogm a of the formation of AH (and cerebrospinal fluid) is that fluid moves isotonically from plasma to AH or cerebrospinal fluid and, therefore, that rate constants k(in) for fluid and for sodium are approximately the same. In the authors' hands, the fluid constant tvas modestly high er than for sodium. This holds for normal function and also for the re duced k(in) for fluid and sodium after carbonic anhydrase inhibition. The k(in) for neither flow nor sodium was affected by pilocarpine. Sur prisingly, however, timolol, which reduces flow, had no effect on Naentry.