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Sildenafil reduces pressure and pulmonary resistance and increases susceptibility of pulmonary arteries to nitric oxide in primary pulmonary arterial hypertension

Sildenafil reduces pressure and pulmonary resistance and increases susceptibility of pulmonary arteries to nitric oxide in primary pulmonary arterial hypertension

Przeglad Lekarski 62(2): 135-138

Primary pulmonary arterial hypertension (PPH) is a rare disease of undetermined origin and fatal prognosis. A better prognosis is associated with at least 20% reduction of either pulmonary artery pressure or pulmonary vascular resistance ("responders") in acute vasodilatory trials. Prostacycline (PGI2) or nitric oxide (NO) administration promises valuable results. NO is one of the most powerful vasodilating agents, endogenously produced by endothelial cells. It migrates from these cells to smooth muscle cells and stimulates production of cGMP, that induces smooth muscle relaxation. cGMP is hydrolyzed by 5-phopshodiesterase (PDE-5). Several papers documenting hypotensive effect in pulmonary circulation of specific PDE5 inhibitor--sildenafil (Viagra--Pfizer) have been published recently. We present a case report of a 26 year old female patient with PPH--"nonresponder" in a trial with NO--and NO responder after sildenafil administration. Initial values were: mean pulmonary artery pressure (mPAP) was 58 mmHg, pulmonary vascular resistance was 10.9 Wood's units. mPAP and PVR during NO inhalation (40 ppm) decrease from 62 to 54 mmHg and from 11.4 to 10.3 Wood's units, respectively. Measurements performed 60 minutes after 50 mg of sildenafil orally disclosed a 19% reduction of mPAP and 21% reduction of PVR. NO inhalation caused further decrease of both parameters: mPAP was decreased for additional 28% and PVR for additional 36% in comparison to initial results. Neither peripheral hypotension nor other side effects were observed. A month-long administration of sildenafil in a dose 2 x 25 mg daily reduced mPAP and PVR to values reported for the acute trial. Physical capability improved also. It was assessed as increased distance in a six-minute-walk test (280 vs. 400 m in the first week of treatment, and 330 m in a fourth week of treatment). Echocardiography showed moderate decrease of right ventricle and right atrium diameters, along with decrease of the degree of relative tricuspid regurgitation with unchanged maximal velocity of regurgitant wave. Specific PDE-5 inhibitors might be an attractive alternative in the treatment of pulmonary hypertension in case the above noted observations are confirmed.

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Accession: 050310328

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PMID: 16095162

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