Angiotensin II receptor antagonists (ARBs) are widely used antihypertensive agents with excellent tolerability and evidence for reduction of the risk of fatal and non-fatal stroke. Nitric oxide (NO) has many vascular actions and commercially available nitrates (e.g. isosorbide mononitrate) are indicated for the treatment of angina but not for blood pressure (BP) control despite being effective in lowering BP, particularly systolic BP. A potential for additive or synergistic effect of the two agents is supported by preclinical and clinical studies suggesting the involvement of the angiotensin II type 1 receptor (AT1-R) in endothelial dysfunction and interactions between RAAS and NO signaling pathways. As part of a joint research program with NicOx, we have sought to demonstrate that linking of NO donors to ARBs will deliver superior BP lowering and may also impart the many beneficial cardiovascular (CV) effects of NO leading to greater CV event reduction. This presentation will cover the design, synthesis and biological evaluation of a novel series of NO-ARBs.

Nitric oxide donating angiotensin II receptor antagonists for the treatment of hypertension

245th National Meeting (2013)

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