The potential of stimulating nitric oxide formation in the treatment of hypertension

ABSTRACT

Introduction: Hypertension is a leading cause of morbidity and mortality worldwide. A major pathophysiological factor contributing to hypertension is reduced nitric oxide (NO) bioavailability. Strategies to address this pathophysiological mechanism could offer significant advantages.

Areas covered: In this review we aimed at examining a variety of drugs (statins, beta-adrenergic receptor blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, angiotensin II type-1 receptor blockers) used to treat hypertension and other cardiovascular diseases, particularly with respect to their potential of increasing NO bioavailability and activity in the cardiovascular system. There is now evidence supporting the notion that many cardiovascular drugs activate NO signaling or enhance NO bioavailability as a contributing mechanism to their beneficial cardiovascular effects. Moreover, other drugs may attenuate NO inactivation by superoxide and other reactive oxygen species by exerting antioxidant effects. More recently, the NO oxidation products nitrite and nitrate have been acknowledged as sources of NO after recycling back to NO. Activation of the nitrate-nitrite-NO pathway is an alternate pathway that may generate NO from both anions and exert antihypertensive effects.

Expert opinion: In this review, we provide an overview of the possible mechanisms by which these drugs enhance NO bioavailability and help in the therapy of hypertension.

KEYWORDS:

• Hypertension
• nitric oxide
• nitrite
• nitrate
• nitric oxide synthase

Article highlights

• As NO plays an essential vasodilatory role, reduction of its bioavailability may contribute to the pathogenesis and/or maintenance of hypertension. Therefore, it is important to investigate potential strategies to synthesize NO and treat hypertension;

• Antioxidants increase the bioavailability of NO and its vasodilatory effects by improving the antioxidant defenses against oxidative stress;

• Statins, beta-adrenergic receptor blockers, angiotensin converting enzyme inhibitors and angiotensin II type-1 receptor blockers activate NO signaling or enhance NO bioavailability as a contributing mechanism to their beneficial cardiovascular effects;

• Activation of the nitrate-nitrite-NO is an alternate pathway to generate NO from both anions and exerts antihypertensive effects.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.