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Thus, impaired production or reduced bioavailability of NO predisposes to the onset of different cardiovascular (CV) diseases. Alterations in the redox balance associated with excitation\u2013contraction coupling have been identified in heart failure (HF), thus contributing to contractile abnormalities and arrhythmias. For its ability to influence cell proliferation and angiogenesis, NO may be considered a therapeutic option for the management of several CV diseases. Several clinical studies and trials investigated therapeutic NO strategies for systemic hypertension, atherosclerosis, and\/or prevention of in stent restenosis, coronary heart disease (CHD), pulmonary arterial hypertension (PAH), and HF, although with mixed results in long-term treatment and effective dose administered in selected groups of patients. Tadalafil, sildenafil, and cinaguat were evaluated for the treatment of PAH, whereas vericiguat was investigated in the treatment of HF patients with reduced ejection fraction. 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