Hypertension Knowledge Centre
Angiotensin II Antagonists
Renoprotection: the role of eprosartan
Angiotensin II mediated mechanisms appear to be important in the pathogenesis of renal hypertension,61 but there is also evidence that hyperactivity of the sympathetic nervous system may also play a role.62 Eprosartan has a higher affinity than other AIIAs for presynaptic angiotensin II receptors, which may be especially beneficial in patients with chronic renal failure.
Neumann et al (2004) assessed the effect of eprosartan (600mg daily for six weeks) on blood pressure and sympathetic activity in eleven hypertensive stable patients with chronic renal failure (BP>145/90mmHg and creatinine clearance 30-70 ml/min).61 To maintain a normovolemic state, six patients received diuretics throughout the study. Sympathetic activity was assessed by measuring muscle sympathetic nerve activity (MSNA) at baseline and during treatment.
In untreated patients, blood pressure, heart rate, plasma renin activity and MSNA were all higher than in matched controls. After six weeks of treatment with eprosartan, there were statistically significant reductions in mean arterial pressure (-12%, p<0.001) and in MSNA (-23%, p<0.001); heart rate was reduced and plasma renin activity was increased.
In this study, mean arterial pressure and MSNA became identical to controls when the centrally-acting sympatholytic agent moxonidine was added to the eprosartan regimen (figure 27). This combination addresses the fact that angiotensin II stimulates sympathetic activity locally by enhancing synaptic release of norepinephrine, and centrally by increasing sympathetic outflow. Eprosartan inhibits the local synaptic effects by blocking the presynaptic angiotensin II receptors, whilst moxonidine inhibits the central effects by stimulating imidazoline I1 receptors located in the rostral ventrolateral medulla (RVLM) of the brainstem. Angiotensin II receptors are present within the RVLM, and it is not yet known whether these are also affected by eprosartan.
Figure 27: Mean muscle sympathetic nerve activity (MSNA) in nine hypertensive patients with chronic renal failure, who were given eprosartan alone or in combination with moxonidine. Controls were healthy age-matched persons (n=22). Adapted from 61
Frank et al (2003) investigated the renoprotective effects of eprosartan (600mg/day for 7 days) in a double-blind, placebo-controlled, crossover study in 10 normotensive and 14 borderline hypertensive patients during cardiopulmonary stress testing.63 Disturbances of cardiopulmonary baroreceptors induced by lower body negative pressure did not result in any change in glomerular filtration rate (GFR) in patients treated with eprosartan, whereas GFR was significantly decreased in patients receiving placebo (p<0.05).