Am J Physiol Heart Circ Physiol 285: H631-H636, 2003.
First published May 15, 2003; doi:10.1152/ajpheart.00111.2003
0363-6135/03 $5.00
Nitric oxide regulates retinal vascular tone in humans
Guido T. Dorner,1,2
Gerhard Garhofer,1,2
Barbara Kiss,1,2
Elzbieta Polska,2
Kaija Polak,1,2
Charles E. Riva,4 and
Leopold Schmetterer1,3
Departments of 1Clinical Pharmacology and
2Ophthalmology and 3Institute
of Medical Physics, University of Vienna Medical School, Vienna A-1090,
Austria; and 4Institut de Recherche en Ophthalmologie,
CH-1950 Sion, Switzerland
Submitted 10 February 2003
; accepted in final form 4 May 2003
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ABSTRACT
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The purpose of the present study was to investigate the contribution of
basal nitric oxide (NO) on retinal vascular tone in humans. In addition, we
set out to elucidate the role of NO in flicker-induced retinal vasodilation in
humans. Twelve healthy young subjects were studied in a three-way crossover
design. Subjects received an intravenous infusion of either placebo or
NG-monomethyl-L-arginine (L-NMMA; 3
or 6 mg/kg over 5 min), an inhibitor of NO synthase. Thereafter, diffuse
luminance flicker was consecutively performed for 16, 32, and 64 s at a
frequency of 8 Hz. The effect of L-NMMA on retinal arterial and
venous diameter was assessed under resting conditions and during the hyperemic
flicker response. Retinal vessel diameter was measured with a Zeiss retinal
vessel analyzer. L-NMMA significantly reduced arterial diameter (3
mg/kg: –2%; 6 mg/kg: –4%, P < 0.001) and venous
diameter (3 mg/kg: –5%; 6 mg/kg: –8%, P < 0.001).
After placebo infusion, flicker induced a significant increase in retinal
vessel diameter (P < 0.001). At a flicker duration of 64 s,
arterial diameter increased by 4% and venous diameter increased by 3%.
L-NMMA did not abolish these hyperemic responses but blunted venous
vasodilation (P = 0.017) and arterial vasodilation (P =
0.02) in response to flicker stimulation. Our data indicate that NO
contributes to basal retinal vascular tone in humans. In addition, NO appears
to play a role in flicker-induced vasodilation of the human retinal
vasculature.
retinal vessel diameter; human retinal blood flow; retinal vessel analyzer; luminance flicker
NITRIC OXIDE (NO) is a potent endothelium-derived vasodilator
that plays a major role in the control of ocular blood flow
(25,
42). The role of NO in the
maintenance of choroidal vascular tone has been shown in a variety of animal
(9,
21,
25,
28,
29,
51) and human studies
(27,
39). The role of NO in the
control of retinal blood flow is less clear. Administration of NO synthase
inhibitors reduced retinal blood flow in some
(10,
18,
43) but not in all animal
studies (9,
30). NO also appears to be
involved in the vasodilation induced by flicker stimulation. This has been
shown in the optic nerve head
(5,
24) and the retina
(24) of the cat.
To date, there are no data on the role of NO in the regulation of human
retinal blood flow available. The purpose of the present study was to
elucidate the role of NO in the maintenance of basal vascular retinal tone in
humans. In addition, we investigated the possible role of NO in the hyperemic
response to flickering light in the retina. Retinal arterial and venous
diameter were therefore compared during placebo infusion and during infusion
of NG-monomethyl-L-arginine
(L-NMMA), a competitive inhibitor of NO synthase. This was done
during resting conditions as well as during flicker periods.
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METHODS
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Subjects. The study protocol was approved by the Ethics Committee
of Vienna University School of Medicine and followed the guidelines of the
Declaration of Helsinki. Twelve healthy male (age range: 20–32 yr, mean
± SD: 25.6 ± 2.1 yr) nonsmoking volunteers signed a written
informed consent and had to pass a screening examination that included medical
history, a physical examination, 12-lead electrocardiogram, and complete blood
count, with differential, clinical chemistry, and coagulation tests, urine
drug screen, hepatitis B and C and human immunodeficiency virus antibody
tests, and an ophthalmic examination. Inclusion criteria were normal
ophthalmic findings, ametropia of <3 diopters, and anisometropia of <1
diopter.
Experimental design. The NO dependence of retinal vessel diameters
was studied in a placebo-controlled three-way crossover design using two doses
of L-NMMA. For this purpose, the subject's pupils were dilated with
tropicamide eye drops (Mydriaticum Agepha; Vienna, Austria). Twenty minutes
later, baseline measurements of systemic blood pressure (SBP) and pulse rate
were performed. Thereafter, a 5-min bolus infusion of physiological saline
solution (placebo) was intravenously administered. Immediately after the end
of this infusion, retinal vessel diameter was continuously measured with a
Zeiss retinal vessel analyzer (RVA) for 352 s. Meanwhile, diffuse luminance
flickering light was applied consecutively for 16, 32, and 64 s
(11). Before and after each
flicker period, 60 s of baseline recording was scheduled (see
Fig. 1). After a 45-min resting
period, L-NMMA (Clinalfa AG; Läufelfingen, Switzerland) was
administered as a bolus over 5 min in a dose of 3 mg/kg. The flicker stimulus
was then reapplied following the time schedule described above. After a
further 45-min resting period, the flicker stimuli were applied again after an
intravenous infusion of 6 mg/kg L-NMMA. Blood pressure was
monitored in 5-min intervals during the study period, and pulse rate was
recorded continuously. Retinal vessel diameters were evaluated by an observer
who was masked with respect to the treatment before the flicker
experiments.
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Fig. 1. Vessel diameter obtained with the Zeiss retinal vessel analyzer in a
healthy subject during the flicker periods of 16, 32, and 64 s. The response
of the diameter of a major inferior temporal retinal vein is depicted. The
bars indicate the start and duration of the consecutive flicker periods.
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Zeiss retinal vessel analyzer. The Zeiss RVA (Zeiss FF 450, Jena,
Germany) comprises a fundus camera, videocamera, real-time monitor, and
personal computer with analyzing software for the accurate determination of
retinal arterial and venous diameter
(3). The fundus is imaged onto
the charge-coupled device chip of the videocamera and digitized using a frame
grabber (image capture rate was set to 25 frames/s). The fundus image can be
inspected on the real-time monitor and, if necessary, stored on videotape
(S-VHS). Evaluation of the retinal vessel diameters can either be done on-line
or off-line from the recorded videotapes.
Because of the absorbing properties of hemoglobin, each blood vessel has a
specific transmittance profile. Measurement of retinal vessel diameters is
based on adaptive algorithms using these specific profiles. To select a region
of interest, the user defines a rectangle on the screen of the real-time
monitor. This window can either include a retinal artery, a retinal vein, or
both. Vessel diameters can be recorded as a function of time as well as a
function of the position along the vessel, and the system is capable to
automatically correct for small eye movements.
In the present study, major inferior temporal arteries or veins were
studied. The distance from the optic disc was between 1 and 2 disc
diameters.
Flicker stimulus with a Grass PS-2 Photo Stimulation model. The
flickering light was delivered through the illumination pathway of the fundus
camera. The maximum luminance of the full field flicker was 
2.5 x
10–5 µJ ·
cm–2 · flash–1.
The flash duration was 30 µs. To avoid that the flickering light itself
interferes with the diameter measurement procedure, the light of the fundus
camera and that of the flicker stimulation was separated by an interference
filter with a center wavelength of 590 nm and a bandwidth of 10 nm in the
illumination pathway of the fundus camera. Hence, the eye was illuminated with
light-containing wavelengths between 580 and 600 nm at a retinal irradiance of
200 µW/cm2. This window was chosen because in this
wavelength range the contrast between blood vessels and the surrounding tissue
is optimal. A second matching interference filter was placed in front of the
videocamera, and a 550-nm low-pass cutoff filter was placed in front of the
flickering light source. With this technique, the flicker stimulus is clearly
perceived by the subject under study but is not detected with the videocamera.
This allows for constant contrast in the fundus image throughout the flicker
experiments (32).
Systemic cardiovascular parameters. SBP, diastolic blood pressure,
and mean arterial blood pressure (MAP) were measured on the upper arm by an
automated oscillometric device (HP-CMS patient monitor, Hewlett-Packard; Palo
Alto, CA). Pulse rate was automatically recorded from a finger pulse oxymetric
device (HP-CMS patient monitor).
Data analysis. The effect of NO synthase inhibition and the effect
of flicker on retinal vessel diameters was determined. In addition, we
assessed the effect of NO synthase inhibition on the flicker response of
vessel diameter. The mean retinal vessel diameter as averaged from the 15 s
preceding the start of the flicker period was defined as the baseline diameter
with regard to flicker independently of whether L-NMMA or placebo
had been administered before the recording. These values were also taken to
assess the effect of L-NMMA on retinal vessel diameter. The flicker
response was defined as the difference between the last 5, 10, and 20 s of the
flicker period for 16, 32, and 64 s of flicker, respectively, and the baseline
diameter and was expressed as the percent change from baseline.
Results are presented as means ± SE. The effect of L-NMMA
and flicker on the outcome variables was assessed with repeated-measures
ANOVA. P = 0.05 was considered as the level of significance.
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RESULTS
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The effects of L-NMMA on systemic cardiovascular parameters are
presented in Table 1. As
expected, L-NMMA caused a dose-dependent increase in MAP (3 mg/kg:
6 ± 2%; 6 mg/kg: 11 ± 2%, P < 0.001) and a decrease
in pulse rate (3 mg/kg: 6 ± 2%; 6 mg/kg: 12 ± 3%, P =
0.003). The effect of NO synthase inhibition on retinal vessel diameter is
depicted in Fig. 2. This
presentation of the time course of retinal vessel diameters does not include
the response to the flicker periods, which is shown in
Fig. 3. After infusion of
L-NMMA, we observed a decrease in retinal arterial (P <
0.001) and venous (P < 0.001) diameters, which was again dose
dependent. L-NMMA (3 mg/kg) caused a 2.1 ± 0.6% reduction in
the diameter of the artery and a 5.3 ± 0.5% reduction in the diameter
of the vein. The decrease in retinal arterial (–3.8 ± 0.8%) and
venous (–7.9 ± 1.1%) diameter in response to 6 mg/kg
L-NMMA was more pronounced.
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Fig. 2. Effect of placebo or 3 or 6 mg/kg
NG-monomethyl-L-arginine (L-NMMA) on
retinal vessel diameter size. The measurements were taken 1 min after the end
of the 5-min drug infusion period. A: arterial diameter; B:
venous diameter. Data are presented as means ± SE (n = 12
subjects). * Significant changes vs. baseline.
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Fig. 3. The changes in arterial and venous diameter as induced by flickering light
of 16-(A), 32-(B), and 64-s (C) duration. The
effect is depicted after pretreatment with placebo, with 3 mg/kg
L-NMMA, and with 6 mg/kg L-NMMA. Data are presented as
means ± SE (n = 12 subjects). * Significant changes vs.
baseline.
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Effect of flickering light. A typical flicker response as obtained
in a healthy subject is shown in Fig.
1. A response to diffuse luminance flicker was observed in all
subjects under study. As shown in Fig.
3, the diameter response was highly significant (P <
0.001 for all periods) but not different between the different flicker
periods.
L-NMMA significantly blunted the response in retinal veins
during flicker (Fig. 3; 16 s:
P = 0.049; 32 s: P = 0.011; 64 s: P = 0.017).
Flicker (64 s) caused a venous diameter increase of 3.3 ± 0.4% after
placebo infusion, 2.0 ± 0.5% after administration of 3 mg/kg
L-NMMA, and 1.4 ± 0.4% after administration of 6 mg/kg
L-NMMA. Flicker responses in retinal arteries were also reduced
when L-NMMA was administered
(Fig. 3; 16 s: P =
0.034; 32 s: P = 0.054; 64 s: P = 0.02). The response of
retinal arteries to flicker stimulation at 64 s was 4.1 ± 0.4% during
placebo infusion. This response was reduced during administration of 3 mg/kg
L-NMMA (2.4 ± 0.7%) as well as during administration of 6
mg/kg L-NMMA (2.0 ± 0.5%).
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DISCUSSION
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The present investigation is the first human study to show that NO has an
important role in the regulation of retinal vascular tone in humans. On the
one hand, NO synthase inhibition significantly reduced retinal artery and vein
diameter, which indicates that basal NO contributes to retinal tone in healthy
subjects. Reduced retinal vessel diameters were observed, although
L-NMMA caused a significant increase in systemic blood pressure and
consequently in ocular perfusion pressure. This effect was more pronounced in
retinal veins but also significant in retinal arteries. On the other hand,
inhibition of NO synthase significantly blunted the hyperemic response to
flicker in retinal vessels, which indicates that NO has a role in
flicker-induced vasodilation. The systemic and retinal hemodynamic effects of
L-NMMA were dose dependent.
The effectiveness of the selected dose of L-NMMA in blocking NO
synthase to a considerable degree is evidenced from several arguments. In the
present study, L-NMMA produced a significant increase in MAP and a
decrease in pulse rate in the subjects under study, which indicates that the
drug induced peripheral vasoconstriction. This is in keeping with previous
clinical trials using comparable doses of L-NMMA
(19,
23,
44). In other human studies, a
reduction in renal (1,
2,
49), choroidal
(27,
37,
39), and cerebral blood flow
(48) was observed. Moreover,
intravenous L-NMMA significantly blunted the vasodilator effects of
insulin, histamine, and hypercapnia
(38,
40,
42) and decreased the
concentration of NO in exhaled air
(27,
39).
The contribution of NO to basal retinal tone is compatible with a number of
previous in vitro and animal studies. Immunoreactivity for NO synthase has
been found in endothelial cells of retinal and choroidal blood vessels and in
pericytes of retinal capillaries
(6,
35). In isolated ophthalmic
artery segments, inhibition of NO synthase produced endothelium-dependent
contractions (50), whereas NO
induced relaxation in retinal pericytes
(17). Conflicting results were
published regarding the effect of intravenous administration of NO synthase
inhibitors on retinal blood flow. A reduction in retinal blood flow
(16,
18,
43) as well as a lack of
effect on retinal perfusion (9,
30) were reported. These
differences may be caused by the selected doses of the drugs, interspecies
differences, or anesthetic differences. Preretinal
(10) and intravitreal
(15) administration of NO
synthase inhibitors caused retinal arteriolar vasoconstriction, although the
latter study indicates that the retinal vasomotor effects elicited by hypoxia,
hypercapnia, and hypotension are not mediated through NO.
In the present study, flicker induced retinal vasodilation in arteries and
veins. An increase in human retinal blood flow after flicker has previously
been suggested based on a blue-field entoptic study
(36) and on direct measurement
of retinal vessel diameter
(14). In addition, several
animal experiments using the microsphere technique
(24) or laser-Doppler
flowmetry (5,
26,
34,
46) revealed ocular
vasodilation in response to flicker. Hence, like in the brain, blood flow in
the eye seems to be coupled to neural activity. This hypothesis is supported
by the observations that the K+ concentration increases near the
optic nerve head during flicker
(4). Elevated glucose
consumption and lactate formation in the retina are additional indicators for
increased metabolic need during stimulation
(47).
NO appears to be a mediator of the retinal vasodilator response to flicker.
Whether other non-NO-independent mechanisms contribute to the hyperemic
response cannot be answered based on the present study, because the degree of
NO synthase inhibition achieved with the selected doses of L-NMMA
at the level of ocular circulation cannot be estimated. There is, however,
evidence from animal experiments that other mechanisms than augmented NO
production, such as an increase in K+ production, could contribute
to flicker-induced ocular vasodilation
(4). The source of the NO
involved in control of retinal hemodynamics remains to be elucidated. The
present study does not answer this question, because L-NMMA is a
nonspecific inhibitor of NO synthase, which blocks endothelial and neuronal NO
synthase.
A variety of procedures have been proposed for the investigation of retinal
vessel diameter (7,
8,
12,
14,
33,
45). Although vessel diameter
is not necessarily an indicator of blood flow through an organ, its
measurement is an important tool in the study of blood flow regulation. The
present study indicates that the Zeiss RVA is suitable for the on-line
investigation of retinal vessel diameter in vivo. The test/retest
reproducibility of the measurements is high
(31). The fact that the small
changes as induced by L-NMMA and flicker could be detected with
this system again demonstrates the high sensitivity of the method.
Compared with other methods, the system has several advantages. On the one
hand, the continuous nature of measurements enables the assessment of very
quick responses of the retinal vasculature in real time. The continuous
recording of vessel diameters also enables the investigation of the frequency
distribution of caliber oscillations. The RVA could therefore also be used to
study vasomotion in human retinal vessels. Moreover, the instrument allows
determination of vessel diameters along a vessel segment. Hence, in patients
with retinal vascular disease, regions of altered retinal reactivity within a
vessel could be detected with this system. For pharmacodynamic studies, the
reproducibility of measurements may even be increased compared with the
present trial, if only diastolic values are included for analysis
(13).
A limitation of the present study is that we did not measure intraocular
pressure (IOP). We (22) have,
however, previously shown that L-NMMA in the selected doses does
not affect IOP. Another limitation of the present study is that changes in
retinal arterial and venous diameter as assessed with the RVA do not
necessarily reflect changes in retinal vascular tone. Particularly, we cannot
entirely exclude that part of the reduction in retinal vessel diameters is due
to the increase in MAP after administration of L-NMMA and not due
to local inhibition in NO. At least in retinal arteries, this appears
unlikely, because even greater changes in MAP as induced either by isometric
exercise (13) or by tyramine
(20) did not affect retinal
arterial diameters. In retinal veins the situation may be different, because
the decrease in diameter may in part represent a passive vasoconstriction due
to increased retinal vascular resistance after L-NMMA
administration. This may also explain why the response in retinal veins was
more pronounced than in retinal arteries.
In conclusion, we have shown that NO has an important role in the control
of basal retinal vascular tone as well as in flicker-induced retinal
vasodilation in humans.
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DISCLOSURES
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This study was supported by Austrian "Fonds zur Förderung der
Wissenschaftlichen Forschung" Project P14262
[GenBank]
and Swiss National Science
Foundation Project P32-53785.
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FOOTNOTES
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Address for reprint requests and other correspondence: L. Schmetterer, Dept.
of Clinical Pharmacology, Waehringer Guertel 18-20, Vienna A-1090, Austria
(E-mail:
leopold.schmetterer{at}univie.ac.at).
The costs of publication of this article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section 1734
solely to indicate this fact.
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REFERENCES
|
|---|
- Bech JN,
Nielsen CB, Ivarsen P, Jensen KT, and Pedersen EB. Dietary sodium affects
systemic and renal hemodynamic response to NO inhibition in healthy humans.
Am J Physiol Renal Physiol 274:
F914–F923, 1998.[Abstract/Free Full Text]
- Bech JN,
Nielsen CB, and Pedersen EB. Effects of systemic NO synthesis inhibition
on RPF, GFR, UNa, and vasoactive hormones in humans. Am J Physiol
Renal Fluid Electrolyte Physiol 270:
F845–F851, 1996.[Abstract/Free Full Text]
- Blum M,
Bachmann K, Wintzer D, Riemer T, Vilser W, and Strobel J. Noninvasive
measurement of the Bayliss effect in retinal autoregulation.
Graefes Arch Clin Exp Ophthalmol
237: 296–300,
1999.[Web of Science][Medline]
- Buerk DG, Riva
CE, and Cranstoun SD. Frequency and luminance dependent blood flow and
K+ ion changes during flicker stimuli in cat optic nerve head.
Invest Ophthalmol Vis Sci 36:
2216–2227, 1995.[Abstract/Free Full Text]
- Buerk DG, Riva
CE, and Cranstoun SD. Nitric oxide has a vasodilatory role in cat optic
nerve head during flicker. Microvasc Res
52: 13–26,
1996.[Web of Science][Medline]
- Chakravarthy U,
Stitt AW, McNally J, Bailie JR, Hoey EM, and Duprex P. Nitric oxide
synthase activity and expression in retinal capillary endothelial cells and
pericytes. Curr Eye Res 14:
285–294, 1995.[Web of Science][Medline]
- Chen HC, Patel
V, Wiek J, Rassam SM, and Kohner EM. Vessel diameter changes during the
cardiac cycle. Eye 8:
97–103, 1994.[Medline]
- Delori FC,
Fitch KA, Feke GT, Deupree DM, and Weiter JJ. Evaluation of micrometric
and densitometric methods for measuring the width of retinal vessel images on
fundus photographs. Graefes Arch Clin Exp Ophthalmol
226: 393–399,
1988.[Web of Science][Medline]
- Deussen A,
Sonntag M, and Vogel R. L-Arginine derived nitric oxide: a
major determinant of uveal blood flow. Exp Eye Res
57: 129–134,
1988.
- Donati G,
Pournaras CJ, Munoz JL, Poitry S, Poitry-Yamate CL, and Tsacopoulos M.
Nitric oxide controls arteriolar tone in the retina of the miniature pig.
Invest Ophthalmol Vis Sci 36:
2228–2237, 1995.[Abstract/Free Full Text]
- Dorner GT,
Garhoefer G, Huemer KH, Riva CE, Wolzt M, and Schmetterer L. Hyperglycemia
affects flicker induced vasodilation in the retina of healthy subjects.
Vision Res. 43:
1495–1500, 2003.[Web of Science][Medline]
- Dumskyj MJ,
Aldington SJ, Dore CJ, and Kohner EM. The accurate assessment of changes
in retinal vessel diameter using multiple frame electrocardiograph
synchronised fundus photography. Curr Eye Res
15: 625–632,
1996.[Web of Science][Medline]
- Dumskyj MJ,
Eriksen JE, Dore CJ, and Kohner EM. Autoregulation in the human retinal
circulation: assessment using isometric exercise, laser Doppler velocimetry,
and computer assisted image analysis. Microvasc Res
51: 378–392,
1996.[Web of Science][Medline]
- Formaz F, Riva
CE, and Geiser M. Diffuse luminance flicker increases retinal vessel
diameter in humans. Curr Eye Res
16: 1252–1257,
1997.[Web of Science][Medline]
- Gidday JM and
Zhu Y. Nitric oxide does not mediate autoregulation of retinal blood flow
in newborn piglets. Am J Physiol Heart Circ Physiol
269: H1065–H1072,
1995.[Abstract/Free Full Text]
- Granstam E,
Wang L, and Bill A. Vascular effects of endothelin-1 in the cat;
modification by indomethacin and L-NAME. Acta Physiol
Scand 148:
165–176, 1993.[Web of Science][Medline]
- Haefliger IO,
Zschauer A, and Anderson DR. Relaxation of retinal pericyte contractile
tone through the nitric oxide-cyclic guanosine monophosphate pathway.
Invest Ophthalmol Vis Sci 35:
991–997, 1994.[Abstract/Free Full Text]
- Harino S,
Nishimura K, Kitanishi K, Suzuki M, and Reinach P. Role of nitric oxide in
mediating retinal blood flow regulation in cats. J Ocul Pharmacol
Ther 15:
295–303, 1999.[Web of Science][Medline]
- Haynes WG, Noon
JP, Walker BR, and Webb DJ. L-NMMA increases blood pressure in
man. Lancet 342:
931–932, 1993.[Web of Science][Medline]
- Jandrasits K,
Luksch A, Söregi G, Dorner GT, Polak K, and Schmetterer L. Effect of
noradrenaline on retinal blood flow in healthy subjects.
Ophthalmology 109:
291–295, 2002.[Web of Science][Medline]
- Kiel JW.
Modulation of choroidal autoregulation in the rabbit. Exp Eye
Res 69:
413–429, 1999.[Web of Science][Medline]
- Kiss B,
Dallinger S, Findl O, Rainer G, Eichler HG, and Schmetterer L.
Acetazolamide-induced cerebral and ocular vasodilation in humans is
independent of nitric oxide. Am J Physiol Regul Integr Comp
Physiol 276:
R1661–R1667, 1999.[Abstract/Free Full Text]
- Koller-Stametz J, Matulla B, Wolzt M, Müller M, Entlicher J,
Eichler HG, and Schmetterer L. Role of nitric oxide in exercise-induced
vasodilation in man. Life Sci
62: 1035–1043,
1998.[Web of Science][Medline]
- Kondo M, Wang
L, and Bill A. The role of nitric oxide in hyperaemic response to flicker
in the retina and optic nerve in cats. Acta Ophthalmol
Scand 75:
232–235, 1997.[Web of Science][Medline]
- Koss MC.
Role of nitric oxide in maintenance of basal anterior choroidal blood flow in
rats. Invest Ophthalmol Vis Sci
39: 559–564,
1998.[Abstract/Free Full Text]
- Koss MC.
Functional role of nitric oxide in regulation of ocular blood flow.
Eur J Pharmacol 374:
161–174, 1999.[Web of Science][Medline]
- Luksch A, Polak
K, Beier C, Polska E, Wolzt M, Dorner GT, Eichler HG, and Schmetterer L.
Effects of systemic NO-synthase inhibition on choroidal and optic nerve head
blood flow in healthy subjects. Invest Ophthalmol Vis
Sci 41:
3080–3084, 2000.[Abstract/Free Full Text]
- Mann RM, Riva
CE, Stone RA, Barnes GE, and Cranstoun SD. Nitric oxide and choroidal
blood flow regulation. Invest Ophthalmol Vis Sci
36: 925–930,
1995.[Abstract/Free Full Text]
- O'Brien C,
Kelly PAT, and Ritchie IM. Effect of chronic inhibition of nitric oxide
synthase on ocular blood flow and glucose metabolism in the rat. Br
J Ophthalmol 81:
68–71, 1997.[Abstract/Free Full Text]
- Ostwald P,
Goldstein IM, Pachnanda A, and Roth S. Effect of nitric oxide synthase
inhibition on blood flow after retinal ischemia in cats. Invest
Ophthalmol Vis Sci 36:
2396–2403, 1995.[Abstract/Free Full Text]
- Polak K, Dorner
GT, Kiss B, Polska E, Findl O, Rainer G, Eichler HG, and Schmetterer L.
Evaluation of the new Zeiss retinal vessel analyzer. Br J
Ophthalmol 84:
1285–1290, 2000.[Abstract/Free Full Text]
- Polak K,
Schmetterer L, and Riva CE. Influence of flicker frequency on
flicker-induced changes of retinal vessel diameter. Invest
Ophthalmol Vis Sci 43:
2721–2726, 2002.[Abstract/Free Full Text]
- Rassam SMB,
Patel V, Brinchmann-Hansen O, Engvold O, and Kohner EM. Accurate vessel
width measurement from the fundus photographs: a new concept. Br J
Ophthalmol 78:
24–29, 1994.[Abstract/Free Full Text]
- Riva CE, Harino
S, Shonat RD, and Petrig BL. Flicker evoked increase in optic nerve head
blood flow in anesthetized cats. Neurosci Lett
128: 291–296,
1991.[Web of Science][Medline]
- Roufail E,
Stringer M, and Rees S. Nitric oxide synthase immunoreactivity and NADPH
diaphorase staining are colocalised in neurons closely associated with
vasculature in rat and human retina. Brain Res
684: 36–46,
1995.[Web of Science][Medline]
- Scheiner AJ,
Riva CE, Kazahaya K, and Petrig BL. Effect of flicker on macular blood
flow assessed by the blue field technique. Invest Ophthalmol Vis
Sci 35:
3436–3441, 1994.[Abstract/Free Full Text]
- Schmetterer L,
Findl O, Fasching P, Ferber W, Strenn K, Breiteneder H, Adam H, Eichler HG,
and Wolzt M. Nitric oxide and ocular blood flow in patients with IDDM.
Diabetes 46:
653–658, 1997.[Abstract]
- Schmetterer L,
Krejcy K, Findl O, Strenn K, Graselli U, Kastner J, Eichler HG, and Wolzt
M. Role of nitric oxide in the O2 and CO2
responsiveness of cerebral and ocular circulation in humans. Am J
Physiol Regul Integr Comp Physiol 273:
R2005–R2012, 1997.[Abstract/Free Full Text]
- Schmetterer L,
Krejcy K, Kastner J, Wolzt M, Gouya G, Findl O, Lexer F, Breiteneder H,
Fercher AF, and Eichler HG. The effect of systemic nitric oxide-synthase
inhibition on ocular fundus pulsations in man. Exp Eye
Res 64:
305–312, 1997.[Web of Science][Medline]
- Schmetterer L,
Müller M, Fasching P, Diepolder C, Gallenkamp A, Zanaschka G, Findl O,
Strenn K, Mensik C, Tschernko E, Eichler HG, and Wolzt M. Renal and ocular
hemodynamic effects of insulin. Diabetes
46: 1868–1874,
1997.[Abstract]
- Schmetterer L and Polak K. Role of nitric oxide in the control of ocular blood flow.
Prog Ret Eye Res 20:
823–847, 2001.[Web of Science][Medline]
- Schmetterer L,
Wolzt M, Graselli U, Findl O, Strenn K, Simak S, Kastner J, Eichler HG, and
Singer E. NO-synthase inhibition in the histamine headache model.
Cephalalgia 17:
175–182, 1997.[Web of Science][Medline]
- Seligsohn EE and Bill A. Effects of NG-nitro-L-arginine
methyl ester on the cardiovascular system of the anaesthetised rabbit and on
the cardiovascular response to thyrotropin-releasing hormone. Br J
Pharmacol 109:
1219–1225, 1993.[Web of Science][Medline]
- Stamler JS, Loh
E, Roddy M, Currie KE, and Creager MA. Nitric oxide regulates basal
systemic and pulmonary vascular resistance in healthy humans.
Circulation 89:
2035–2040, 1994.[Abstract/Free Full Text]
- Suzuki Y.
Direct measurement of retinal vessel diameter: comparison with
microdensometric methods based on fundus photographs. Surv
Ophthalmol 39:
S57–S65, 1995.[Medline]
- Van Toi V and
Riva CE. Variations of blood flow at the optic nerve head induced by
sinusoidal flicker stimulation in cats. J Physiol
482: 189–202,
1995.[Abstract/Free Full Text]
- Wang L and Bill
A. Effects of constant and flickering light on retinal metabolism in
rabbits. Acta Ophthalmol Scand
75: 227–231,
1997.[Web of Science][Medline]
- White RP, Deane
C, Vallance P, and Marhus HS. Nitric oxide synthase inhibition in humans
reduces cerebral blood flow but no the hyperemic response to hypercapnia.
Stroke 29:
467–472, 1998.[Abstract/Free Full Text]
- Wolzt M,
Schmetterer L, Ferber W, Artner E, Mensik C, Eichler HG, and Krejcy K.
Effect of nitric oxide synthase inhibition on renal hemodynamics in man:
reversal by L-arginine. Am J Physiol Renal
Physiol 272:
F178–F182, 1997.[Abstract/Free Full Text]
- Yao K, Tschudi
M, Flammer J, and Lüscher TF. Endothelium-dependent regulation of
vascular tone of the porcine ophthalmic artery. Invest Ophthalmol
Vis Sci 32:
1791–1798, 1991.[Abstract/Free Full Text]
- Zagvazdin YS,
Fitzgerald ME, Sancesario G, and Reiner A. Neural nitric oxide mediates
Edinger-Westphal nucleus evoked increase in choroidal blood flow in the
pigeon. Invest Ophthalmol Vis Sci
37: 666–672,
1996.[Abstract/Free Full Text]
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