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Drugs Targeting RAAS in the Treatment of Hypertension and Other Cardiovascular Diseases

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Pathophysiology and Pharmacotherapy of Cardiovascular Disease

Abstract

Drugs with diversified structure and class target the RAAS cascade at various levels. Beginning with the inhibition of renin from the juxtaglomerular cells of the kidney, it extends to the blockade of formation and actions of its principal component, Ang II, and its effector, aldosterone and its synthesis. Although all of them are very efficacious in combating overactivation of RAAS, ACE inhibitors and ARBs stand out in the armamentarium of RAAS inhibitors. All of them are effective in lowering blood pressure but differ from each other in potency, pharmacokinetic properties and additional pharmacologic actions that are contributed by their unique functional groups. Therapeutic uses of RAAS blockers stem from the dynamics of the complex intertwined downstream signaling molecules that interact to contribute beyond blood pressure control. Thus, some of the ACE inhibitors and ARBs are also indicated in the treatment of heart failure, left ventricular dysfunction following myocardial infarction, and nephropathy in T2DM, reducing the risk of cardiovascular mortality, nonfatal myocardial infarction, and the risk of developing heart failure. Several studies have investigated the dual inhibition of the RAAS in hypertension and heart failure with an outcome of more adverse events without an increase in benefit. While considering Ang II and aldosterone escape processes during ACE inhibitors and ARBs therapies, RAAS at the base level can be halted using aldosterone receptor antagonists for the management of hypertension and heart failure. In this chapter, we review and discuss the pharmacologic interference with the functioning of the RAAS at different levels in the axis, a major therapeutic approach in the treatment of hypertension and other cardiovascular disease.

The opinions expressed herein are those of GJ and do not necessarily reflect those of the US Food and Drug Administration.

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Acknowledgment

We greatly acknowledge and express our gratitude to Dr. Khin Maung-U of US FDA for his expertise and constructive suggestions to improve this chapter.

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Authors and Affiliations

  1. Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100, Bedong, Kedah Darul Aman, Malaysia

    Pitchai Balakumar PhD

  2. Division of Cardiovascular and Renal Products, Center for Drug Evaluation and Research, US Food and Drug Administration (FDA), 10903 New Hampshire Avenue Building 22, Room 4128, Silver Spring, MD, 20993-0002, USA

    Gowraganahalli Jagadeesh PhD

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  1. Center for Drug Evaluation and Research Division of Cardiovascular and Renal Products, US Food and Drug Administration, Silver Spring, Maryland, USA

    Gowraganahalli Jagadeesh

  2. Pharmacology Unit, AIMST University, Bedong, Malaysia

    Pitchai Balakumar

  3. Center for Drug Evaluation and Research Division of Cardiovascular and Renal Products, US Food and Drug Administration, Silver Spring, Maryland, USA

    Khin Maung-U

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Balakumar, P., Jagadeesh, G. (2015). Drugs Targeting RAAS in the Treatment of Hypertension and Other Cardiovascular Diseases. In: Jagadeesh, G., Balakumar, P., Maung-U, K. (eds) Pathophysiology and Pharmacotherapy of Cardiovascular Disease. Adis, Cham. https://doi.org/10.1007/978-3-319-15961-4_36

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