Cyclic GMP, sodium nitroprusside and sodium azide reduce aqueous humour formation in the isolated arterially perfused pig eye

Abstract

1 The effect of nitric oxide (NO) on aqueous humour formation (AHF) and intraocular pressure (IOP) was studied using NO donors, sodium azide (AZ) and sodium nitroprusside (SNP). 2 Using the porcine arterially perfused eye preparation, drug effects on AHF and IOP were measured by fluorescein dilution and manometry, respectively. Perfusion pressure of the ocular vasculature was also monitored using digital pressure transducer and pen recorder. 3 L-Arginine (1.0 mM), a precursor of NO, but not D-arginine (1.0 mM), the inactive analogue, produced a significant reduction in AHF (28.5%) and IOP (21.1%). L-NAME (L-nitro-L-arginine) (10-100 mM), an NO synthase inhibitor, had no effect on AHF and IOP. However, L-NAME (100 mM) completely reversed L-arginine's effect. 4 AZ and SNP reduced the AHF and IOP dose-dependently. AZ at 100 nM, 1 and 10 mM reduced AHF by 26.0, 39.7 and 51.7% and IOP by 10.8, 17.3 and 24.0%, respectively. SNP at 1, 10 and 100 mM reduced the AHF by 6.0, 24.2 and 35.4% and IOP by 3.5, 9.5 and 15.5%, respectively. 8-pCPT-cGMP (8-para-chlorophenyl-thioguanosine-3 0 ,5 0 -cyclic guanosine monophosphate, 10 mM), a cGMP analogue, also reduced the AHF (34.9%) and IOP (15.9%). 5 The effects of AZ and SNP on the AHF and IOP were blocked by a soluble guanylate cyclase inhibitor ODQ (10 mM), whereas ODQ alone or combined with 8-pCPT-cGMP had no effect on the AHF and IOP. 6 None of the drugs had any significant effect on ocular vasculature. 7 The reduction of the AHF and IOP in the arterially perfused pig eye by nitrovasodilators is likely to involve the NO-cGMP pathway.

Characterization and Regulation of Gap Junctions in Porcine Ciliary Epithelium

“…5,6,[19][20][21] Recently, we have demonstrated that the stimulation of Isc by cAMP and forskolin in porcine CE 22 are in good agreement with results obtained in human tissue. 23 In this study, we aimed to characterize the expression of Cx isoforms in porcine CE, determine the relative abundance of various Cx, and investigate the functional significance of the most abundant Cx in mediating fluid movement from PE to NPE cells.…”

“…5 These results indicate that the transport mechanisms and regulation of AH secretion may vary among species. Porcine eye may be a good animal model to mimic human ocular conditions because access to human eyes is limited while fresh porcine eyes are readily available; the physical dimensions and anatomic properties of porcine eyeball are similar to those of humans 20,21 ; the electrolyte composition of the AH as well as the characteristics of AH dynamics in pig are similar to those in humans 1,19 ; and the biocompatibility of pig and human eyes has been demonstrated in an artificial corneal graft study. 32 Our recent findings of cAMP-and forskolininduced Isc stimulation in porcine CE 22 are also in good agreement with the results obtained for the human ciliary process, 23 suggesting that pig may be a good animal model for studying AH dynamics.…”

Effect of Nitric Oxide on Anterior Segment Physiology in Monkeys

“…25 Nitric oxide decreases cell volume in the trabecular meshwork and increases OF in porcine eye anterior segments, suggesting that the nitric oxide-induced alterations in cell volume may regulate outflow resistance. 26 IOP and AHF are decreased in isolated pig eyes perfused with nitrovasodilators, 27 suggesting mechanisms independent of ocular vasculature. Systemic administration of L-NAME to rabbits resulted in an increase in MAP, but a dramatic reduction in IOP, possibly due to a reduction in ciliary blood flow sufficient to impair aqueous production.…”

Endothelial Nitric Oxide Synthase-Related Mechanotransduction Changes in Aged Porcine Angular Aqueous Plexus Cells

“…In human eyes, NOS reactivity was enriched in major sites of outflow resistance, including the TM and SC, as well as in collecting channels. 16 The NO-donating compounds effectively decrease conventional outflow resistance, leading to a decrease in IOP and outflow rate in different animal models, including rabbits, [21][22][23][24] pigs, 25 dogs, 22 and monkeys, 22,26 and in perfused postmortem human eyes. 27,28 Our previous study 29 further showed that eNOS/NO is a key regulator of outflow facility and IOP in mice.…”