Effects of losartan on cerebral and ocular circulation in healthy subjects.
OBJECTIVE
The introduction of specific inhibitors of AT1 receptors, such as losartan, has enabled the investigation of the renin-angiotensin-system (RAS) in humans in vivo. We studied the role of the RAS in the cerebral and ocular circulation in healthy subjects. Haemodynamic effects of orally administered losartan were investigated with non-invasive methods.


METHODS
In a placebo-controlled randomized, double-blind two way crossover design losartan (100 mg orally) or placebo was administered in 10 healthy subjects. The effect of losartan was studied at hourly intervals for 8 h. In addition, the effect of losartan on haemodynamic changes induced by exogenous angiotensin II (Ang II) was assessed. Blood flow velocities in the ophthalmic and the middle cerebral artery (OA, MCA) were measured with Doppler sonography. Pulsatile choroidal blood flow was estimated with laser interferometric measurement of fundus pulsation.


RESULTS
Losartan significantly increased fundus pulsation amplitude (+11%, 95% CI: 5 to 16% P<0.0001), tended to increase resistive index in the ophthalmic artery (+12%, 95% CI: 0 to 23%) and tended to decrease mean arterial pressure (-15%, 95% CI: -23 to -1%). Ang II induced effects on cerebral, ocular and systemic haemodynamics were prevented by preceding administration of losartan.


CONCLUSIONS
The present data suggest that Ang II is not a major determinant of cerebral and ocular blood flow in vivo. The observed changes in cerebral and ocular haemodynamic parameters after losartan administration reflect effects on systemic blood pressure.
Matulla
B
B
Department of Clinical Pharmacology, Vienna, Austria.
Streit
G
G
Pieh
S
S
Findl
O
O
Entlicher
J
J
Graselli
U
U
Eichler
H G
HG
Wolzt
M
M
Schmetterer
L
L
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004453:Echoencephalography; D005123:Eye / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D011897:Random Allocation; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D018608:Ultrasonography, Doppler
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D019808:Losartan