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Renin inhibition with aliskiren in hypertension: focus on aliskiren/hydrochlorothiazide combination therapy.

Sureshkumar KK - Vasc Health Risk Manag (2008)

Bottom Line: Renin-angiotensin-aldosterone system (RAAS) plays a crucial role in volume regulation and maintenance of blood pressure.Aliskiren is an orally effective direct renin inhibitor that blocks the generation of angiotensin I from angiotensinogen, the rate limiting step of RAAS activation.Studies have shown equivalent antihypertensive efficacy of aliskiren when compared to existing medications such as HCTZ, ACE inhibitors and ARBs.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology and Hypertension, Allegheny General Hospital, Pittsburgh, PA 15212, USA. ksureshk@wpahs.org

ABSTRACT
Hypertension is a major risk factor for the development of cardiovascular and renal disease. The incidence of hypertension is increasing globally and the rate of blood pressure control remains inadequate. Renin-angiotensin-aldosterone system (RAAS) plays a crucial role in volume regulation and maintenance of blood pressure. Pathological activation of RAAS results in chronic hypertension and consequent end organ damage. Most patients with hypertension require combination therapy using agents with complimentary mechanisms of action. Hydrochlorothiazide (HCTZ) together with an agent blocking the RAAS such as an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) are widely used effective anti-hypertensive therapy. Aliskiren is an orally effective direct renin inhibitor that blocks the generation of angiotensin I from angiotensinogen, the rate limiting step of RAAS activation. Studies have shown equivalent antihypertensive efficacy of aliskiren when compared to existing medications such as HCTZ, ACE inhibitors and ARBs. Aliskiren has also been tested in combination therapies. The current review aims to look at the efficacy of aliskiren therapy in hypertension and the evidence for using aliskiren in combination with HCTZ.

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Renin-angiotensin-aldosterone system and the sites of blockade. Thick arrows indicate main pathways, thin arrows denote alternative pathways and dashed arrows show sites of blockade.Abbreviations: ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; AT-R, angiotensin receptor; DRI, direct renin inhibitor; LVH, left ventricular hypertrophy.
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f1-vhrm-4-1205: Renin-angiotensin-aldosterone system and the sites of blockade. Thick arrows indicate main pathways, thin arrows denote alternative pathways and dashed arrows show sites of blockade.Abbreviations: ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; AT-R, angiotensin receptor; DRI, direct renin inhibitor; LVH, left ventricular hypertrophy.

Mentions: A schematic of the RAAS is depicted in Figure 1. Renin is an aspartic protease generated and released from the juxtaglomerular cells in the kidney. The renin molecule has two homologous lobes and the cleft between the lobes contain the active site (Danser and Deinum 2005). Under the influence of renin, angiotensinogen, the only know substrate of renin is cleaved to generate the decapeptide angiotensin I (Ang I). This is the rate-limiting step of RAAS activation. In the presence of angiotensin converting enzyme (ACE), Ang I is converted into the octapeptide hormone angiotensin II (Ang II), a powerful vasoconstrictor that mediates its activity through the type-1 angiotensin II (AT1) receptor. Binding of Ang II to AT1 receptor increases BP, and promotes aldosterone secretion from adrenal cortex, sodium reabsorption in renal proximal tubules, and catecholamine release from pre-synaptic nerve endings and adrenal medulla (Kim and Iwao 2000). Pathological activation of RAAS can result in hypertension with consequent end-organ damage.


Renin inhibition with aliskiren in hypertension: focus on aliskiren/hydrochlorothiazide combination therapy.

Sureshkumar KK - Vasc Health Risk Manag (2008)

Renin-angiotensin-aldosterone system and the sites of blockade. Thick arrows indicate main pathways, thin arrows denote alternative pathways and dashed arrows show sites of blockade.Abbreviations: ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; AT-R, angiotensin receptor; DRI, direct renin inhibitor; LVH, left ventricular hypertrophy.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2663460&req=5

f1-vhrm-4-1205: Renin-angiotensin-aldosterone system and the sites of blockade. Thick arrows indicate main pathways, thin arrows denote alternative pathways and dashed arrows show sites of blockade.Abbreviations: ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; AT-R, angiotensin receptor; DRI, direct renin inhibitor; LVH, left ventricular hypertrophy.
Mentions: A schematic of the RAAS is depicted in Figure 1. Renin is an aspartic protease generated and released from the juxtaglomerular cells in the kidney. The renin molecule has two homologous lobes and the cleft between the lobes contain the active site (Danser and Deinum 2005). Under the influence of renin, angiotensinogen, the only know substrate of renin is cleaved to generate the decapeptide angiotensin I (Ang I). This is the rate-limiting step of RAAS activation. In the presence of angiotensin converting enzyme (ACE), Ang I is converted into the octapeptide hormone angiotensin II (Ang II), a powerful vasoconstrictor that mediates its activity through the type-1 angiotensin II (AT1) receptor. Binding of Ang II to AT1 receptor increases BP, and promotes aldosterone secretion from adrenal cortex, sodium reabsorption in renal proximal tubules, and catecholamine release from pre-synaptic nerve endings and adrenal medulla (Kim and Iwao 2000). Pathological activation of RAAS can result in hypertension with consequent end-organ damage.

Bottom Line: Renin-angiotensin-aldosterone system (RAAS) plays a crucial role in volume regulation and maintenance of blood pressure.Aliskiren is an orally effective direct renin inhibitor that blocks the generation of angiotensin I from angiotensinogen, the rate limiting step of RAAS activation.Studies have shown equivalent antihypertensive efficacy of aliskiren when compared to existing medications such as HCTZ, ACE inhibitors and ARBs.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology and Hypertension, Allegheny General Hospital, Pittsburgh, PA 15212, USA. ksureshk@wpahs.org

ABSTRACT
Hypertension is a major risk factor for the development of cardiovascular and renal disease. The incidence of hypertension is increasing globally and the rate of blood pressure control remains inadequate. Renin-angiotensin-aldosterone system (RAAS) plays a crucial role in volume regulation and maintenance of blood pressure. Pathological activation of RAAS results in chronic hypertension and consequent end organ damage. Most patients with hypertension require combination therapy using agents with complimentary mechanisms of action. Hydrochlorothiazide (HCTZ) together with an agent blocking the RAAS such as an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) are widely used effective anti-hypertensive therapy. Aliskiren is an orally effective direct renin inhibitor that blocks the generation of angiotensin I from angiotensinogen, the rate limiting step of RAAS activation. Studies have shown equivalent antihypertensive efficacy of aliskiren when compared to existing medications such as HCTZ, ACE inhibitors and ARBs. Aliskiren has also been tested in combination therapies. The current review aims to look at the efficacy of aliskiren therapy in hypertension and the evidence for using aliskiren in combination with HCTZ.

Show MeSH
Related in: MedlinePlus