New Hope for Treatment-Resistant Hypertension (June 2010)

Clinical Potential of Combined Organic Nitrate and Phosphodiesterase Type 5 Inhibitor in Treatment-Resistant Hypertension

Nitric oxide donor drugs (eg, isosorbide mononitrate; ISMN)and phosphodiesterase 5 inhibitors (eg, sildenafil) have antihypertensiveproperties, and the combination can markedly reduce blood pressure(BP). The objective of this "proof-of-concept" study was toinvestigate the effect on BP of a combination of single oraldoses of sildenafil (50 mg) and ISMN (10 mg) in patients withtreatment-resistant hypertension. Six subjects with treatment-resistanthypertension were included, and their usual antihypertensivemedication was continued during the study. Sildenafil alone,ISMN alone, and the combination all reduced brachial and centralaortic BPs compared with placebo. The combination of sildenafiland ISMN produced the largest fall in BP (maximum brachial BPreduction of 26/18 mm Hg compared with placebo), without producingsignificant adverse effects. ISMN, alone and in combinationwith sildenafil, also reduced arterial wave reflection and centralBP. From the above findings the authors concluded that in patients with treatment-resistant hypertensionmaintained on their usual antihypertensive treatment, sildenafilgiven alone and ISMN given alone both acutely reduced BP. Therewas additional BP reduction when these drugs were given in combination.In this therapeutically challenging group of patients, the combinationof an NO donor drug and a phosphodiesterase 5 inhibitor mayrepresent an effective treatment. Longer studies in larger numbersof patients are now justified.

REFERENCE:

http://hyper.ahajournals.org/cgi/content/abstract/HYPERTENSIONAHA.109.147686v1