Effects of Sildenafil on Retinal Blood Flow and Flicker-Induced Retinal Vasodilatation in Healthy Subjects

Polak, Kaija; Wimpissinger, Barbara; Berisha, Fatmire; Georgopoulos, Michael; Schmetterer, Leopold

doi:10.1167/iovs.03-0177

Cited by 52 publications

(33 citation statements)

References 27 publications

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“…The results corroborate the ones presented by POLAK et al (2003), which evaluated the same variables in men treated with a single dose of the drug. They do not differ from the ones presented by PACHE et al (2002), which notifi ed discrete decrease of the mean arterial pressure, with no evidences of heart or intraocular pressure changes.…”

Section: Discussionsupporting

confidence: 90%

“…In this study, the increased speed of blood fl ow in the retina was statistically signifi cant, with decreased time to the onset of the arteriovenous stage at days 7 th and 15 th after treatment with sildenafi l citrate, which agrees with the increased vascular fl ow in human choroid and retina, reported by POLAK et al (2003) and HARRIS et al (2008). The increase can be attributed to the dilation of retinal arterial vessels, by increased release of nitric oxide, through PDE5 inhibition (WRIGHT, 2006).…”

Section: Discussionsupporting

confidence: 85%

“…Potential effects on the retina, heart and blood pressure were the targets of investigations (PACHE et al, 2002 Ciência Rural, v.44, n.8, ago, 2014. POLAK et al, 2003;AMERI et al, 2008;FORESTA et al, 2008;CORDELL et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, PDE-5 inhibitors may also act by inhibiting the type-6 phosphodiesterase (PDE-6) present in the retina, with complications to the vision (ASHBY, 2006). There is evidence that the sildenafi l citrate increases retinal blood circulation and it is speculated that the event is a consequence of increased blood fl ow, per vasodilation, similar to what happens within the corpus cavernosum sphere (GRUNWALD et al, 2001;POLAK et al, 2003;FORESTA et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Sildenafil citrate on retrobulbar and retinal circulation of rabbits

et al. 2014

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sildenafil citrate on retrobulbar and retinal circulation of rabbits

et al. 2014

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“…In addition, the use of the B-type natriuretic peptide nesiritide (Natrecor) in patients with congestive heart failure (Zinch et al, 2003) may represent another potential combination therapy with PDE5 inhibitors. More recently, sildenafil has been shown to increase retinal blood flow without increasing intraocular pressure, suggesting that PDE5 inhibitors may be useful for retinal ischemic diseases (Polak et al, 2003). In circulatory disturbances in which endothelial dysfunction is regarded as a primary cause (peripheral arterial occlusive disease, diabetes), PDE5 inhibitors may be of use alone or in combination with other therapeutic agents.…”

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confidence: 99%

Cyclic GMP and Phosphodiesterase 5 Inhibitor Therapies: What's on the Horizon?: Fig. 1.

Lincoln¹

2004

Mol Pharmacol

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A little more than 6 years ago, the first therapeutic agent targeting cyclic nucleotide phosphodiesterases (PDEs) for the treatment of erectile dysfunction (ED) was introduced into clinical medicine (Boolell et al., 1996). The PDE5 inhibitor sildenafil (Viagra) was the first orally active, effective therapy for the treatment of ED by virtue of its capacity to inhibit cyclic GMP hydrolysis in penile cavernosal and arterial smooth muscle. This Perspective will focus on a "bench-tobedside" view of PDE5 inhibitors, including comments relating to the emergence of newer PDE5 inhibitor drugs, and the extraordinary explosion of research into novel therapeutic uses of PDE5 inhibitors. Figure 1 reviews the role of PDE5 in the metabolism of cyclic GMP and how PDE5 inhibition alters the activity of cellular pathways regulated by cyclic GMP. Cyclic GMP is synthesized in cells by guanylyl cyclases. There are two types of guanylyl cyclase: a membrane-bound, particulate form that is activated by circulating natriuretic peptides and guanylins and a soluble, cytosolic form that is activated by nitric oxide (NO). NO diffuses from cells that express NO synthases, such as neurons and endothelial cells, into target cells, such as smooth muscle cells, to activate soluble guanylyl cyclase. Cyclic GMP interacts with cellular receptors, which, in smooth muscle, include the serine/threonine kinase cyclic GMP-dependent protein kinase (PKG) and the cyclic AMP specific phosphodiesterase 3 (PDE3). The binding of cyclic GMP activates PKG but inhibits PDE3 activity. In cavernosal tissue in particular, but also in most vascular and nonvascular smooth muscle, PDE5 represents a major cyclic GMP-hydrolyzing activity. PDE5 itself is activated by phosphorylation catalyzed by PKG. Phosphorylation increases cyclic GMP binding to noncatalytic cyclic GMP binding GAF domains; this results in the activation of cyclic GMP hydrolysis at distinct catalytic sites. The interactions between PKG and PDE5 insure that cyclic GMP levels do not accumulate too rapidly in the cell. The catalytic cyclic GMP binding sites on PDE5, but not the GAF sites, bind PDE5 inhibitors with high affinity to block cyclic GMP hydrolysis. Therefore, a greater degree of activation of PKG occurs in the cell, and in smooth muscle, enhanced PKG-dependent phosphorylation of a variety of protein substrates inhibits contraction.In this issue of Molecular Pharmacology, Blount et al. (2004) assess the binding properties of the newer PDE5 inhibitors, vardenafil (Levitra) and tadalafil (Cialis), and compare the properties of these compounds with those of sildenafil. The order of potency for inhibition of PDE5 correlates closely with the binding affinity of the drugs for the catalytic sites. Because each of these inhibitors competes with the other inhibitors for access to PDE5, each must bind in the same manner to PDE5. Of particular interest regarding the potent biological effects of these compounds is that cyclic GMP addition increased the binding affinity (inhibitory activity) of the newer inhi...

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Tadalafil-Induced Subretinal and Choroidal Hemorrhage in a Patient With an Unsuspected Uveal (Choroidal and Ciliary Body) Melanoma

Abramson¹

2006

Arch Ophthalmol

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Effects of Sildenafil on Retinal Blood Flow and Flicker-Induced Retinal Vasodilatation in Healthy Subjects

Cited by 52 publications

References 27 publications

Sildenafil citrate on retrobulbar and retinal circulation of rabbits

Sildenafil citrate on retrobulbar and retinal circulation of rabbits

Cyclic GMP and Phosphodiesterase 5 Inhibitor Therapies: What's on the Horizon?: Fig. 1.

Tadalafil-Induced Subretinal and Choroidal Hemorrhage in a Patient With an Unsuspected Uveal (Choroidal and Ciliary Body) Melanoma

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