Nitric oxide does not mediate autoregulation of retinal blood flow
in newborn pig.
Gidday, Jeffrey M., and Yun Zhu.
Departments of Neurology and Neurological Surgery, Ophthalmology
and Visual Sciences, and Cell Biology and Physiology, Washington
University School of Medicine, St. Louis, MO 63110
APStracts 2:0112H, 1995.
Isoflurane-anesthetized newborn pigs were used to test the hypothesis
that nitric oxide mediates autoregulatory dilations of retinal
arterioles. Fundus images were monitored by videomicroscopy at 310x,
and stimulus-induced changes in retinal arteriolar diameter were
measured by on-line image analysis. Dilatative responses to systemic
hypoxia (PaO2=20-30 mmHg), hypotension (MABP = 40 mmHg), or hyper
-capnia (PaCO2 = 70-85 mmHg) were assessed following intravitreal
microsuffusion of the nitric oxide synthase inhibitor L-N6
-monomethyl-arginine (L-NMMA) over the observed arterioles. Twenty
-five nmol L-NMMA constricted arterioles by 24+/-2 % (p<0.01; n=17);
a significant constriction (14+/-2 %) was still observed 80 min after
drug administration (n=5). Complete nitric oxide synthase inhibition
at this dose was indicated by the findings that co-administration of
2.5 [mu]mol L-arginine reversed this constriction within 17+/-2 min
(n=3), that L-NMMA, but not D-NMMA, completely inhibited the 20+/-3 %
(p<0.01) arteriolar dilation induced by intravitreal acetylcholine
(7.5 nmol; n=4), and that no additional constriction was evidenced
after administration of a 10-fold greater concentration of L-NMMA
(n=8). However, despite the prominent arteriolar constriction induced
by L-NMMA under baseline conditions, increases in retinal arteriolar
diameter still occurred in response to hypoxia (n=5), hypotension
(n=4), or hypercapnia (n=5) in animals pretreated with 50 nmol L
-NMMA; these responses did not differ significantly from arteriolar
dilations observed in untreated control animals (n=16) subjected to
the same stimuli. These findings indicate that resting arteriolar
tone in retina is controlled by endogenous nitric oxide biosynthesis,
but autoregulatory dilatative responses to hypoxia, hypotension, and
hypercapnia occur independent of nitric oxide participation.
Received 21 December 1994; accepted in final form 21 March 1995.
APS Manuscript Number H1122-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 4 April 1995.