Characterization of angiotensin-II effects on cerebral and ocular circulation by noninvasive methods.
OBJECTIVE
The role of the renin-angiotensin-system (RAS) in the cerebral and ocular circulation is still a matter of controversy. In vitro and animal data lead to partially contradicting results. However, direct investigation of locally generated angiotensin II (Ang II) in humans is not possible in vivo. Hence, we hypothesised that it might be possible to characterize local effects of Ang II by comparing systemic and local haemodynamic parameters during exogenous Ang II infusion.


METHODS
In a placebo-controlled, double-blind, two-way cross over study blood flow velocities in the middle cerebral and the ophthalmic artery and ocular fundus pulsations were measured during stepwise increasing doses of Ang II in 10 healthy subjects. Blood flow velocities were assessed by Doppler sonography, fundus pulsation amplitudes (FPA), which estimate local pulsatile ocular blood flow were measured by laser interferometry. Additionally, systemic blood pressure and pulse rate were measured.


RESULTS
Ang II dose-dependently decreased resistive index (RI) and increased mean flow velocities (MFV) in both arteries. Fundus pulsation amplitude was dose-dependently decreased by Ang II, whereas mean arterial pressure (MAP) was significantly increased. Pulse pressure amplitude (PPA) was not affected by Ang II administration. There was a high degree of correlation between changes in RIs and the analogously calculated PPA/systolic blood pressure during Ang II infusion, which indicates that the changes in RI after Ang II administration can be attributed to changes in systemic haemodynamics. Calculation of total local ocular blood flow from fundus pulsation amplitudes and changes in flow pulsatility in the ophthalmic artery further argue against significant blood flow changes after Ang II administration.


CONCLUSIONS
Interpretation of data from Doppler sonography and laser interferometry must be done very carefully when concomitant changes in systemic haemodynamics occur. RI cannot necessarily be taken as an index of distal vascular resistance in these cases and changes in MFV can be caused by changes in vessel diameter or in blood flow. Moreover, FPA cannot be taken as a measure of ocular blood flow if no additional data on flow pulsatility are available. The combination of our systemic and local haemodynamic data indicates that cerebral and ocular circulation are comparably insensitive to changes in local Ang II concentrations. Fundus pulsation and blood flow velocity measurements indicate that neither choroidal nor optic nerve head blood flow are significantly affected by administration of Ang II.
Krejcy
K
K
Department of Clinical Pharmacology, Institute of Pharmacology, University of Vienna, Austria.
Wolzt
M
M
Kreuzer
C
C
Breiteneder
H
H
Schütz
W
W
Eichler
H G
HG
Schmetterer
L
L
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002536:Cerebral Arteries / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005123:Eye / Q000098:blood supply* / Q000000981:diagnostic imaging; D005654:Fundus Oculi; D006801:Humans; D008297:Male; D009880:Ophthalmic Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D017585:Ultrasonography, Doppler, Transcranial; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D000804:Angiotensin II