Ocular hypotensive mechanism of intravitreally injected brain natriuretic peptide in rabbit.
OBJECTIVE
To determine whether brain natriuretic peptide (BNP) affects intraocular pressure (IOP), aqueous humor dynamics, and cyclic guanosine monophosphate (cGMP) concentration in the aqueous humor of the rabbit eye.


METHODS
Twenty microliters of 10(-4) M and 10(-5) M (2 nmol, 0.2 nmol) BNP or atrial natriuretic peptide (ANP) were injected intravitreally into rabbit eyes, after which the IOP was measured using a pneumatonometer. Aqueous humor dynamics were studied at approximately 6 hours after the intravitreal injection of 2 nmol BNP. Aqueous humor flow was measured by fluorophotometry, and outflow facility was measured by the two-level constant pressure perfusion method, whereas uveoscleral outflow was measured by the fluorescein isothiocyanate-dextran perfusion method. The concentration of cGMP in the aqueous humor at 6 hours after injection of 2 or 0.2 nmol BNP also was measured by enzyme immunoassay.


RESULTS
Intravitreal administration of BNP or of ANP caused a decrease in IOP, with a maximum effect at approximately 6 hours after the injection. Total outflow facility in eyes treated with 2 nmol BNP increased by 29%, although the aqueous humor flow and uveoscleral outflow did not show significant changes. The concentration of cGMP in the aqueous humor increased significantly in BNP-treated eyes.


CONCLUSIONS
Intravitreal injection of BNP into rabbit eyes reduced IOP because of an increase in the outflow facility. Brain natriuretic peptide also increased the concentration of cGMP in the aqueous humor. It is probable that BNP-activated guanylate cyclase induced an upregulation of cGMP in the aqueous humor.
Takashima
Y
Y
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Japan.
Taniguchi
T
T
Yoshida
M
M
Haque
M S
MS
Yoshimura
N
N
Honda
Y
Y
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D019793:Fluorescein; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D015590:Fluorophotometry; D007267:Injections; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D015814:Ocular Hypotension / Q000139:chemically induced / Q000503:physiopathology*; D011817:Rabbits; D014065:Tonometry, Ocular; D014822:Vitreous Body
D005452:Fluoresceins; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D019793:Fluorescein