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Enalapril and losartan reduce sympathetic hyperactivity in patients with chronic renal failure
Inge H H T Klein1, Gerry Ligtenberg, P Liam Oey
1Department of Nephrology, University Medical Center Utrecht, The Netherlands.
Insights
This study found that both ACE inhibitors and AngII receptor blockers equally reduced blood pressure and sympathetic nerve activity in hypertensive patients with chronic renal failure. These findings suggest AngII-mediated mechanisms are key in sympathetic hyperactivity in these patients.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Hypertensive patients with chronic renal failure (CRF) often exhibit sympathetic hyperactivity.
- Understanding the role of the renin-angiotensin system (RAS) in this hyperactivity is crucial for effective treatment.
Purpose of the Study:
- To compare the effects of angiotensin (Ang)-converting enzyme (ACE) inhibition and AngII receptor blockade on blood pressure (BP) and muscle sympathetic nerve activity (MSNA) in hypertensive CRF patients.
- To investigate the contribution of AngII-mediated mechanisms to sympathetic hyperactivity in this population.
Main Methods:
- A randomized study in ten stable hypertensive CRF patients.
- Patients received either enalapril (ACE inhibitor) or losartan (AngII receptor blocker) for 6 weeks each, with a washout period in between.
- Measurements included 24-h ambulatory BP, plasma renin activity (PRA), baroreceptor sensitivity, and MSNA.
Main Results:
- Both enalapril and losartan significantly reduced average 24-h BP and MSNA compared to baseline.
- No significant differences were observed between enalapril and losartan in their effects on BP and MSNA.
- A correlation was found between the reduction in BP and the reduction in MSNA during both treatments.
- Baroreceptor sensitivity remained unaffected by either treatment.
Conclusions:
- In hypertensive CRF patients, both ACE inhibitors and AngII receptor blockers are equally effective in reducing BP and MSNA.
- These findings support the hypothesis that AngII-mediated pathways play a significant role in the sympathetic hyperactivity observed in hypertensive CRF patients.
- The similar effects of ACE inhibition and AngII blockade on MSNA suggest a common downstream mechanism influenced by AngII.
Abstract:
The aim of this study was to compare the effects on BP and sympathetic activity of chronic treatment with an angiotensin (Ang)-converting enzyme (ACE) inhibitor and an AngII receptor blocker in hypertensive patients with chronic renal failure (CRF). In ten stable hypertensive CRF patients (creatinine clearance, 46 +/- 17 ml/min per 1.73 m(2)), muscle sympathetic nerve activity (MSNA), plasma renin activity (PRA), baroreceptor sensitivity, and 24-h ambulatory BP were measured in the absence of antihypertensive drugs (except diuretics) after 6 wk of enalapril (10 mg orally) and after 6 wk of losartan (100 mg orally). The order of the three phases was randomized. Normovolemia was controlled with diuretics and confirmed with extracellular fluid volume measurements throughout the study. Both enalapril and losartan reduced MSNA (from 33 +/- 10 to 27 +/- 13 and 27 +/- 13 bursts/min, respectively; P < 0.05) and average 24-h BP (from 141 +/- 8/93 +/- 8 to 124 +/- 9/79 +/- 8 and 127 +/- 8/81 +/- 9 mmHg; P < 0.01). PRA was not different during the treatments. The change in BP and the change in MSNA during the treatments were correlated (r = 0.70 and r = 0.63, respectively; both P < 0.05). Baroreceptor sensitivity was not affected by the treatments. This is the first study to compare the effects of ACE inhibition and AngII blockade on MSNA. In hypertensive CRF patients, enalapril and losartan equally reduced BP and MSNA. Differences in modes of action of the two drugs did not result in differences in effects on MSNA, supporting the view that AngII-mediated mechanisms contribute importantly in the pathogenesis of sympathetic hyperactivity in these patients.