Effects of losartan on cerebral and ocular circulation in healthy subjects

Abstract

AimsThe introduction of specific inhibitors of AT 1 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.Keywords: Doppler sonography, fundus pulsation, losartan, angiotensin II, cerebral blood flow, ocular blood flow that Ang II does not play an important role in the regulation Introduction of ocular blood flow [9, 10]. The involvement of the angiotensin renin system in the The renin-angiotensin system (RAS) plays a pivotal role in the regulation of vascular tone. Inhibition of the reninregulation of cerebral and ocular blood flow in vivo in humans is even less well understood. Results with ACE angiotensin system by angiotensin converting enzyme (ACE) inhibitors has been successfully used in the treatment of inhibitors are difficult to interpret, because of the lack of specificity of this class of drugs [11, 12]. We have previously hypertension and congestive heart failure [1, 2]. However, ACE is not very specific and has substrates other than Ang I investigated the effect of intravenous infusion of Ang II on cerebral and ocular haemodynamics in healthy subjects [13] including bradykinin, substance P and neurokinins, which may be responsible for some of the side effects of ACE and observed dose-dependent changes in haemodynamic parameters in the middle cerebral artery, the ophthalmic inhibitors [3]. The development of specific, selective type 1 receptor (AT 1 ) antagonists has therefore attracted much artery, and the choroid. However, careful interpretation of these results argues that these changes were mainly caused interest and its blood pressure lowering efficacy in pa...

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“…The pulsatile fraction of blood flow in the OA was calculated as (MFVϪEDV)/MFV. 16,17 All parameters were determined as mean values over at least three cardiac cycles.…”

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