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Advances in Pharmacologic Modulation of Nitric Oxide in Hypertension

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Abstract

A number of structural and functional mechanisms have been identified in the pathogenesis of hypertensive vascular disease, each of which requires effective therapy to reduce global cardiovascular risk. Hypertension, together with other cardiovascular risk factors, promotes endothelial dysfunction as evidenced by decreased nitric oxide (NO) release and reduced vascular responsiveness to normal vasodilatory stimuli. In addition, the mechanical forces inherent in hypertension activate neurohormonal mechanisms, including the renin-angiotensin system, which modulate vessel wall structure and function. Antihypertensive drugs may have class-specific hemodynamic and physiologic effects that attenuate these vascular disease processes. Pharmacologic approaches that enhance endothelial NO bioavailability have been shown to restore vasodilation while reducing clinical events. These agents improve NO bioavailability by increasing endogenous production through enzymatic mechanisms or by promoting the direct release of NO by its redox congeners in a spontaneous fashion. In this article, we review the basic mechanisms of endothelial dysfunction along with the use and comparative therapeutic benefits of various pharmacologic interventions, with particular emphasis on antihypertensive agents.

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Abbreviations

ACCOMPLISH:

Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension

A-HeFT:

African American Heart Failure Trial

ASCOT:

Anglo-Scandinavian Cardiac Outcomes Trial

CAFE:

Conduit Artery Function Evaluation

ENCORE I:

Elevation of Nifedipine and Cerivastatin on Recovery of Endothelial Function

RALES:

Randomized Aldactone Evaluation Study.

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Disclosure

Dr. R. Preston Mason has received preclinical research funding from Astra Zeneca, Daiichi Sankyo, Forest Research Institute, NicOx, Novartis, Pfizer, and Sanofi Aventis. No other potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Yoshiko Mizuno & R. Preston Mason

  2. Elucida Research LLC, 100 Cummings Center, Suite 135L, Beverly, MA, 01915, USA

    Yoshiko Mizuno, Robert F. Jacob & R. Preston Mason

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  1. Yoshiko Mizuno
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  2. Robert F. Jacob
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Correspondence to R. Preston Mason.

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Mizuno, Y., Jacob, R.F. & Mason, R.P. Advances in Pharmacologic Modulation of Nitric Oxide in Hypertension. Curr Cardiol Rep 12, 472–480 (2010). https://doi.org/10.1007/s11886-010-0142-5

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