THE MECHANISM OF ACTION OF GUANETHIDINE ON AQUEOUS HUMOR DYNAMICS

¹ W. K. Kellogg Foundation Laboratories, The Wilmer Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, and Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, New York

Guanethidine was administered in rabbits either subcutaneously (10-20 mg/kg) or intravitreously (100-200 µg). At varying time intervals after a single injection of guanethidine, the effects on intraocular pressure, outflow facility of aqueous humor, sympathetic amine concentration in the ciliary body and iris tissues of the eye, mean arterial blood pressure and heart rate were studied. Severe hypotension, bradycardia and diarrhea had occurred only after subcutaneous injection of guanethidine. Sympathetic amine depletion in the ocular tissues was similar whether guanethidine was administered subcutaneously or intravitreously. However, the effects of guanethidine on the eyes, apart from amine depletion, were more prominent in the latter series. These included miosis, ptosis, and a fall in intraocular pressure. An increase in outflow of aqueous humor was observed only when guanethidine was introduced directly into the eye. It is postulated that following subcutaneous administration, guanethidine did not penetrate the blood-aqueous barrier, but that when the guanethidine was introduced directly into the eye, it either exerted a direct sympathomimetic action on outflow resistance, or it rendered the outflow mechanism supersensitive to adrenergic substances.