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Direct renin inhibition — a new way of targeting the renin system
Morris J Brown
University of Cambridge, Addenbrooke's Hospital, Cambridge, UK, mjb14{at}medschl.cam.ac.uk
The renin system plays a key role in the pathology of hypertension and is influenced, both directly and indirectly, by most antihypertensive agents. The system is the target of several established classes of antihypertensive agents including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers. Of currently available drugs, only the beta-blockers suppress renin secretion, but these also reduce heart rate and cardiac output. Calcium channel blockers and diuretics cause a modest activation of the renin system secondary to the fall in renal afferent arteriolar pressure and reduction in filtered sodium load. Aliskiren is the first orally available direct inhibitor that blocks the renin system at its rate limiting step and is shown to reduce angiotensin I and II and plasma renin activity.
Key Words: renin aliskiren direct renin inhibitors
References
- Gibbons GH The pathophysiology of hypertension: the importance of angiotensin II in cardiovascular remodeling. Am J Hypertens 1998;11 (11 Pt 2):177S-181S.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Goodfriend TL In: Izzo JL Jr, Black HR, eds. Hypertension Primer: The Essentials of High Blood Pressure. 3rd ed. Philadelphia, Pa; Lippincott Williams & Wilkins; 2003:8-11.
- Arakawa K., Urata H. Hypothesis regarding the pathophysiological role of alternative pathways of angiotensin II formation in atherosclerosis. Hypertension 2000;36:638-41.[Abstract/Free Full Text]
- Luft FC, Mervaala E., Muller DN et al. Hypertension-induced end-organ damage: a new transgenic approach to an old problem. Hypertension 1999;33:212-18.[Abstract/Free Full Text]
- Mezzano S., Droguett A., Burgos ME et al. Renin-angiotensin system activation and interstitial inflammation in human diabetic nephropathy. Kidney Int 2003;64:S64-S70.
- Dzau VJ Tissue renin-angiotensin system in myocardial hypertrophy and failure. Arch Intern Med 1993;153:937-42.[Abstract/Free Full Text]
- Hartman D., Sagnella GA, Chesters CA, MacGregor GA Direct renin assay and plasma renin activity assay compared. Clinical Chemistry 2004;50:2159-61.[Free Full Text]
- Alderman MH, Ooi WL, Cohen H. et al. Plasma renin activity: a risk factor for myocardial infarction in hypertensive patients. Am J Hypertens 1997;10:1-8.[Medline]
[Order article via Infotrieve]
- Brown MJ Matching the right drug to the right patient in essential hypertension. Heart 2001;86:113-20.[Free Full Text]
- Cockcroft JR, Brown MJ Losartan for cardiovascular disease in patient's with and without diabetes in the LIFE study. Lancet 2002;359:2202.[Medline]
[Order article via Infotrieve]
- Williams B., Lacy PS, Thom SM et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation 2006;113: 1213-25.[Abstract/Free Full Text]
- Hood S., Cannon J., Foo R., Brown M. Prevalence of primary hyperaldosteronism assessed by aldosterone/renin ratio and spironolactone testing. Clin Med 2005;5:55-60.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Nguyen G., Delarue F., Burckle C., Bouzhir L., Giller T., Sraer JD Pivotal role of the renin/prorenin J receptor in angiotensin II production and cellular responses to renin. J Clin Invest 2002;109:1417-27.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Ichihara A., Kaneshiro Y., Takemitsu T. et al. Nonproteolytic activation of prorenin contributes to development of cardiac fibrosis in genetic hypertension. Hypertension 2006;47:894-900.[Abstract/Free Full Text]
- Müller DN, Luft FC Direct renin inhibition with aliskiren in hypertension and target organ damage. Clin J Am Soc Nephrol 2006;1:221-8.[Abstract/Free Full Text]
- Azizi M., Menard J., Bissery A. et al. Pharmacologic demonstration of the synergistic effects of a combination of the renin inhibitor aliskiren and the AT1 receptor antagonist valsartan on the angiotensin II-renin feedback interruption. J Am Soc Nephrol 2004;15:3126-33.[Abstract/Free Full Text]
- Weber MA, Giles TD Inhibiting the renin-angiotensin system to prevent cardiovascular diseases: do we need a more comprehensive strategy? Rev Cardiovasc Med 2006;7:45-54.[Web of Science][Medline]
[Order article via Infotrieve]
- Herron J., Mitchell J., Oh B. et al. The novel renin inhibitor aliskiren is not associated with rebound effects on blood pressure or plasma renin activity following treatment withdrawal. J Clin Hypertens 2006;8(5 suppl A):A86-7. Abstract P-193.[CrossRef]
- Kilo C., Taylor A., Tschoepe D. et al. Aliskiren, a novel renin inhibitor for treatment of hypertension, enhances renin system suppression by reducing plasma renin activity alone or in combination with ramipril in patients with diabetes. Abstract presented at WCC/ESC, Barcelona, Spain 2-6 September 2006 (P-789).
- Calhoun D., Chrysant S., Villamil A., Schober B., Hsu H., Prescott MF The novel oral renin inhibitor aliskiren decreasSes plasma renin activity (PRA) and neutralizes hydrochlorothiazide-induced RAAS activation in hypertensive patients. J Clin Hypertens 2006;8(5 suppl A):A77. Abstract P-168.
- Azizi M., Webb R., Nussberger J. et al. Renin inhibition with aliskiren: where are we now, and where are we going? J Hypertens 2006;24:243-56.[Web of Science][Medline]
[Order article via Infotrieve]
Journal of Renin-Angiotensin-Aldosterone System, Vol. 7, No. 2 suppl,
S7-S11 (2006)
DOI: 10.3317/jraas.2006.035

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