Clinical potential of combined organic nitrate and phosphodiesterase type 5
inhibitor in treatment-resistant hypertension.
Author(s): Oliver JJ, Hughes VE, Dear JW, Webb DJ.
Affiliation(s): Clinical Pharmacology Unit, Centre for Cardiovascular Science, University of
Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.
Publication date & source: 2010, Hypertension. , 56(1):62-7
NO donor drugs (eg, isosorbide mononitrate; ISMN) and phosphodiesterase 5
inhibitors (eg, sildenafil) have antihypertensive properties, and the combination
can markedly reduce blood pressure (BP). The objective of this "proof-of-concept"
study was to investigate the effect on BP of a combination of single oral doses
of sildenafil (50 mg) and ISMN (10 mg) in patients with treatment-resistant
hypertension. Six subjects with treatment-resistant hypertension were included,
and their usual antihypertensive medication was continued during the study.
Sildenafil alone, ISMN alone, and the combination all reduced brachial and
central aortic BPs compared with placebo. The combination of sildenafil and ISMN
produced the largest fall in BP (maximum brachial BP reduction of 26/18 mm Hg
compared with placebo), without producing significant adverse effects. ISMN,
alone and in combination with sildenafil, also reduced arterial wave reflection
and central BP. In summary, in patients with treatment-resistant hypertension
maintained on their usual antihypertensive treatment, sildenafil given alone and
ISMN given alone both acutely reduced BP. There was additional BP reduction when
these drugs were given in combination. In this therapeutically challenging group
of patients, the combination of an NO donor drug and a phosphodiesterase 5
inhibitor may represent an effective treatment. Longer studies in larger numbers
of patients are now justified.
Erratum in
Hypertension. 2012 Jul;60(1):e8. Hughes, Victoria E C [added].
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