Skip to main content
PMC home page
The British Journal of Ophthalmology logoLink to The British Journal of Ophthalmology
. 1999 Feb;83(2):162–167. doi: 10.1136/bjo.83.2.162

Effect of isosorbide mononitrate on the human optic nerve and choroidal circulations

J Grunwald 1, A Iannaccone 1, J DuPont 1
PMCID: PMC1722947  PMID: 10396191

Abstract

AIMS—To assess the effects of the nitric oxide donor 5-isosorbide mononitrate (ISMO) on blood flow in the optic nerve head (ON flow) and choroid (Ch flow).
METHODS—Laser Doppler flowmetry was used to measure ON flow and Ch flow in 12 normal subjects by aiming the laser beam at the fovea and at the temporal rim, respectively. In a double masked, randomised, crossover design, each subject received orally on separate days either 20 mg of 5-isosorbide mononitrate (ISMO) or placebo. Ch flow and ON flow were determined monocularly at baseline and 1 hour after dosing. In the last six subjects, additional measurements were obtained at 3 hours. Mean arterial blood pressure (BPm), heart rate, and intraocular pressure (IOP) were monitored, and ocular perfusion pressure (PP) was estimated.
RESULTS—No significant changes in ON flow, PP, IOP, or BPm were observed following placebo. Following ISMO, ON flow increased from baseline by 19.8% (SEM 9.3%) at 1 hour (paired t test, p= 0.058) and by 33.1% (7.5%) at 3 hours (p= 0.007). Compared with the changes following placebo, statistically significant increases in ON flow were observed both at 1 (p=0.050) and 3 hours (p=0.041) after ISMO treatment. Compared with placebo, PP decreased significantly 1 hour after ISMO dosing (p=0.039), mainly as a function of reduced BPm. A significant inverse correlation (R=−0.618; p=0.032) was observed between the percentage changes in PP and ON flow 1 hour following ISMO administration, but not after placebo. No significant change in foveal Ch flow was documented.
CONCLUSIONS—These results suggest that, in normal subjects, ISMO increases significantly ON flow but not Ch flow. The inverse correlation observed between PP and ON flow suggests that the same mechanism(s) responsible for systemic vasodilatation and blood pressure decrease may also cause the ON flow increase.

 Keywords: choroidal circulation; isosorbide mononitrate; laser Doppler flowmetry; nitric oxide; optic nerve head circulation

Full Text

The Full Text of this article is available as a PDF (127.9 KB).

Figure 1  .

Figure 1  

Open in a new tab

Comparison of the percentage changes from baseline in optic nerve head blood flow (ON flow) after placebo and ISMO treatment in each subject. (A) Measurements at 1 hour after dosing (n=12). (B) Measurements at 3 hours after dosing (n=6).    

Figure 2  .

Figure 2  

Open in a new tab

Percentage change in optic nerve head blood flow (ON flow) v percentage change in perfusion pressure (PP) at 1 hour after ISMO (A) and placebo (B). There is a significant correlation after ISMO treatment (R=-0.618; p=0.032), but not following placebo administration (R=0.071; p=0.825).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Buerk D. G., Riva C. E., Cranstoun S. D. Nitric oxide has a vasodilatory role in cat optic nerve head during flicker stimuli. Microvasc Res. 1996 Jul;52(1):13–26. doi: 10.1006/mvre.1996.0040. [DOI] [PubMed] [Google Scholar]
  2. Charness M. E., Liu G. T. Central retinal artery occlusion in giant cell arteritis: treatment with nitroglycerin. Neurology. 1991 Oct;41(10):1698–1699. doi: 10.1212/wnl.41.10.1698. [DOI] [PubMed] [Google Scholar]
  3. FRAYSER R., HICKAM J. B. EFFECT OF VASODILATOR DRUGS ON THE RETINAL BLOOD FLOW IN MAN. Arch Ophthalmol. 1965 May;73:640–642. doi: 10.1001/archopht.1965.00970030642008. [DOI] [PubMed] [Google Scholar]
  4. Flügel C., Tamm E. R., Mayer B., Lütjen-Drecoll E. Species differences in choroidal vasodilative innervation: evidence for specific intrinsic nitrergic and VIP-positive neurons in the human eye. Invest Ophthalmol Vis Sci. 1994 Feb;35(2):592–599. [PubMed] [Google Scholar]
  5. Goldstein I. M., Ostwald P., Roth S. Nitric oxide: a review of its role in retinal function and disease. Vision Res. 1996 Sep;36(18):2979–2994. doi: 10.1016/0042-6989(96)00017-x. [DOI] [PubMed] [Google Scholar]
  6. Grunwald J. E., DuPont J., Dreyer E. B. Effect of chronic nitrate treatment on retinal vessel caliber in open-angle glaucoma. Am J Ophthalmol. 1997 Jun;123(6):753–758. doi: 10.1016/s0002-9394(14)71123-7. [DOI] [PubMed] [Google Scholar]
  7. Haefliger I. O., Flammer J., Lüscher T. F. Nitric oxide and endothelin-1 are important regulators of human ophthalmic artery. Invest Ophthalmol Vis Sci. 1992 Jun;33(7):2340–2343. [PubMed] [Google Scholar]
  8. Haefliger I. O., Zschauer A., Anderson D. R. Relaxation of retinal pericyte contractile tone through the nitric oxide-cyclic guanosine monophosphate pathway. Invest Ophthalmol Vis Sci. 1994 Mar;35(3):991–997. [PubMed] [Google Scholar]
  9. Harino S., Riva C. E., Petrig B. L. Intravenous nicardipine in cats increases optic nerve head but not retinal blood flow. Invest Ophthalmol Vis Sci. 1992 Sep;33(10):2885–2890. [PubMed] [Google Scholar]
  10. Hessemer V., Schmidt K. G. Einfluss des Vasodilators Isosorbiddinitrat auf den okulären Kreislauf. Klin Monbl Augenheilkd. 1996 Mar;208(3):188–195. doi: 10.1055/s-2008-1035194. [DOI] [PubMed] [Google Scholar]
  11. Hessemer V., Schmidt K. G. Influence of the vasodilator drug isosorbide dinitrate on ocular circulation. Arch Ophthalmol. 1997 Mar;115(3):324–327. doi: 10.1001/archopht.1997.01100150326003. [DOI] [PubMed] [Google Scholar]
  12. Hiroishi G., Kobayashi S., Nishimura J., Inomata H., Kanaide H. Differential effects of diltiazem and nitroglycerin on cytosolic Ca2+ concentration and on force in the bovine ophthalmic artery. Invest Ophthalmol Vis Sci. 1996 Dec;37(13):2612–2623. [PubMed] [Google Scholar]
  13. Hutt V., Theodor R., Pabst G., Bonn R., Fritschi E., Jaeger H. Evaluation of bioavailability and pharmacokinetics of two isosorbide-5-mononitrate preparations in healthy volunteers. J Clin Pharmacol. 1992 Jun;32(6):553–557. doi: 10.1177/009127009203200611. [DOI] [PubMed] [Google Scholar]
  14. Kitamura Y., Okamura T., Kani K., Toda N. Nitric oxide-mediated retinal arteriolar and arterial dilatation induced by substance P. Invest Ophthalmol Vis Sci. 1993 Sep;34(10):2859–2865. [PubMed] [Google Scholar]
  15. Kondo M., Wang L., Bill A. The role of nitric oxide in hyperaemic response to flicker in the retina and optic nerve in cats. Acta Ophthalmol Scand. 1997 Jun;75(3):232–235. doi: 10.1111/j.1600-0420.1997.tb00762.x. [DOI] [PubMed] [Google Scholar]
  16. Kuritzky S. Nitroglycerin to treat acute loss of vision. N Engl J Med. 1990 Nov 15;323(20):1428–1428. doi: 10.1056/NEJM199011153232019. [DOI] [PubMed] [Google Scholar]
  17. Mann R. M., Riva C. E., Stone R. A., Barnes G. E., Cranstoun S. D. Nitric oxide and choroidal blood flow regulation. Invest Ophthalmol Vis Sci. 1995 Apr;36(5):925–930. [PubMed] [Google Scholar]
  18. Meyer P., Flammer J., Lüscher T. F. Endothelium-dependent regulation of the ophthalmic microcirculation in the perfused porcine eye: role of nitric oxide and endothelins. Invest Ophthalmol Vis Sci. 1993 Dec;34(13):3614–3621. [PubMed] [Google Scholar]
  19. Neufeld A. H., Hernandez M. R., Gonzalez M. Nitric oxide synthase in the human glaucomatous optic nerve head. Arch Ophthalmol. 1997 Apr;115(4):497–503. doi: 10.1001/archopht.1997.01100150499009. [DOI] [PubMed] [Google Scholar]
  20. Nishimura K., Riva C. E., Harino S., Reinach P., Cranstoun S. D., Mita S. Effects of endothelin-1 on optic nerve head blood flow in cats. J Ocul Pharmacol Ther. 1996 Spring;12(1):75–83. doi: 10.1089/jop.1996.12.75. [DOI] [PubMed] [Google Scholar]
  21. Qi X., Guy J. Localization of NADPH diaphorase/nitric oxide synthase in the optic nerve of the normal guinea pig: a light and electron microscopic study. J Comp Neurol. 1996 Jul 1;370(3):396–404. doi: 10.1002/(SICI)1096-9861(19960701)370:3<396::AID-CNE9>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar]
  22. Riva C. E., Cranstoun S. D., Grunwald J. E., Petrig B. L. Choroidal blood flow in the foveal region of the human ocular fundus. Invest Ophthalmol Vis Sci. 1994 Dec;35(13):4273–4281. [PubMed] [Google Scholar]
  23. Riva C. E., Harino S., Petrig B. L., Shonat R. D. Laser Doppler flowmetry in the optic nerve. Exp Eye Res. 1992 Sep;55(3):499–506. doi: 10.1016/0014-4835(92)90123-a. [DOI] [PubMed] [Google Scholar]
  24. Riva C. E., Titze P., Hero M., Petrig B. L. Effect of acute decreases of perfusion pressure on choroidal blood flow in humans. Invest Ophthalmol Vis Sci. 1997 Aug;38(9):1752–1760. [PubMed] [Google Scholar]
  25. Schaumann W. Pharmacokinetics of isosorbide dinitrate and isosorbide-5-mononitrate. Int J Clin Pharmacol Ther Toxicol. 1989 Sep;27(9):445–453. [PubMed] [Google Scholar]
  26. Sinclair A. M., Hughes A. D., Sever P. S. Effect of nifedipine and glyceryl trinitrate on retinal blood flow in normal subjects. J Hum Hypertens. 1993 Aug;7(4):399–401. [PubMed] [Google Scholar]
  27. Thadani U., Maranda C. R., Amsterdam E., Spaccavento L., Friedman R. G., Chernoff R., Zellner S., Gorwit J., Hinderaker P. H. Lack of pharmacologic tolerance and rebound angina pectoris during twice-daily therapy with isosorbide-5-mononitrate. Ann Intern Med. 1994 Mar 1;120(5):353–359. doi: 10.7326/0003-4819-120-5-199403010-00001. [DOI] [PubMed] [Google Scholar]
  28. Vorwerk C. K., Hyman B. T., Miller J. W., Husain D., Zurakowski D., Huang P. L., Fishman M. C., Dreyer E. B. The role of neuronal and endothelial nitric oxide synthase in retinal excitotoxicity. Invest Ophthalmol Vis Sci. 1997 Sep;38(10):2038–2044. [PubMed] [Google Scholar]
  29. Wizemann A., Maier T., Wizemann V. Wirksamkeit unterschiedlicher Therapieprinzipien bei experimentellen Netzhautgefässverschlüssen. Fortschr Ophthalmol. 1983;80(2):176–178. [PubMed] [Google Scholar]
  30. Yao K., Tschudi M., Flammer J., Lüscher T. F. Endothelium-dependent regulation of vascular tone of the porcine ophthalmic artery. Invest Ophthalmol Vis Sci. 1991 May;32(6):1791–1798. [PubMed] [Google Scholar]
  31. Zagvazdin Y. S., Fitzgerald M. E., Sancesario G., Reiner A. Neural nitric oxide mediates Edinger-Westphal nucleus evoked increase in choroidal blood flow in the pigeon. Invest Ophthalmol Vis Sci. 1996 Mar;37(4):666–672. [PubMed] [Google Scholar]

Articles from The British Journal of Ophthalmology are provided here courtesy of BMJ Publishing Group

RESOURCES