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The effects of orally administered Sildenafil (Viagra) on cerebral circulation in newborn pigs
Author(s) -
Pourcyrous Massroor,
Parfenova Helena,
Leffler Charles W
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a295-b
Subject(s) - sildenafil , vasodilation , cgmp specific phosphodiesterase type 5 , medicine , sodium nitroprusside , cerebral circulation , anesthesia , phosphodiesterase inhibitor , nitric oxide , endocrinology
Objective The phosphodiesterase‐5 (PDE‐5) inhibitor sildenafil citrate (Viagra) recently has begun to be used in patients with pulmonary hypertension. However, the cerebrovascular effects of sildenafil are not known. Methods In anesthetized newborn pigs, closed cranial windows were placed to measure pial arteriolar diameters (PAD) and the brain cGMP production as detected by cGMP level in cortical periarachnoid cerebrovascular fluid (CSF). Sildenafil (1 mg/kg) was given slowly via orogastric tube to minimize the hypotensive effects of the drug. Cerebral vasodilators nitroprusside (cGMP‐dependent) and isoproterenol (cAMP‐dependent) were administered under the cranial windows before and after oral sildenafil. Results Sildenafil resulted in mild dilation of pial arterioles and 3‐fold rise in CSF cGMP level. Pial arteriolar dilation to nitroprusside increased significantly after sildenafil compared to control. However, sildenafil did not change dilation of pial arterioles to isoproterenol. Conclusions Oral sildenafil increased CSF cGMP level, caused dilation of cerebral arterioles, and exaggerated dilation to cGMP‐mediated vasodilator stimuli. These data indicate that oral sildenafil may cross blood‐brain barrier, inhibit brain PDE‐5 activity and have cGMP‐dependent cerebral vascular effects.