The usefulness of selective inhibitors of phosphodiesterase 5 (PDE5) is well known, first
for the treatment of male erectile dysfunction and more recently for pulmonary hypertension. The discovery
that PDE5 is present in the systemic artery endothelium and smooth muscle cells led investigators
to test the extra sexual effects of sildenafil, the first and most investigated PDE5 inhibitor, in diseases
affecting the systemic arteries. Cumulative data from experimental and clinical studies have revealed beneficial effects
of sildenafil on systemic arterial hypertension and its target organs, such as the heart, kidneys and vasculature. An
important effect of sildenafil is reduction of hypertension and improvement of endothelial function in experimental models
of hypertension and hypertensive subjects. Interestingly, in angiotensin-dependent hypertension, its beneficial effects
on endothelial and kidney dysfunctions seem to at least in part be caused by its ability to decrease the levels of angiotensin
II and increase angiotensin 1-7, in addition to improving nitric oxide bioavailability and diminishing reactive oxygen species.
Another remarkable finding on the effects of sildenafil comes from studies in apolipoprotein E knockout mice, a
model of atherosclerosis that closely resembles human atherosclerotic disease. In this review, we focus on the promising
beneficial effects of sildenafil for treating systemic high blood pressure, especially resistant hypertension, and the endothelial
dysfunction that is present in hypertension and atherosclerosis.
Keywords: Atherosclerosis, angiotensin, sildenafil, PDE, endothelial dysfunction, systemic hypertension.
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