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BRIEF COMMUNICATIONS: M. Diomedi, F. Sallustio, B. Rizzato, F. Ferrante, G. Leone, E. Spera, M. Scarfini, and G. Bernardi Sildenafil increases cerebrovascular reactivity: A transcranial Doppler study Neurology 2005; 65: 919-921 [Abstract] [Full text] [PDF]

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Sildenafil increases cerebrovascular reactivity: A transcranial Doppler study

Steven Brenner   (16 January 2006)

Sildenafil may have potential for treatment of cerebral vasospasm in subarachnoid hemorrhage

Marina Diomedi, Fabrizio Sallustio   (16 January 2006)

Sildenafil increases cerebrovascular reactivity: A transcranial Doppler study 16 January 2006
Steven Brenner, St. Louis VA Medical Center and St. Louis University Departments of Neurology Dept. Neuology, VA Med. Center, 915 North Grand, St.Louis, MO 63106 Send Correspondence to journal: Re: Sildenafil increases cerebrovascular reactivity: A transcranial Doppler study SBren20979{at}aol.com Steven Brenner	I read the article by Diomedi [1] et al on sildenafil increasing cerebrovascular reactivity. This finding could have implications for treatment of cerebrovascular conditions such as subarachnoid hemorrhage. Sildenafil a phosphodiesterase V (PDE V) inhibitor relaxes vascular smooth muscle throught a cyclic guanosine monophosphate (cGMP)second messenger, and may act on vascular media to inhibit vasospasm in conditions such as subarachnoid hemorrhage which may cause severe vasospasms with consequent stroke. Subarachnoid hemorrhage(SAH) is associated with impaired nitric oxide (NO) mediated cerebral vasodilatation. An increased rate of cGMP hydrolysis by PDE V may be a factor contributing to impairment of NO mediated cerebral vasodilatation from relaxation of vascular smooth muscle after SAH. [2] PDE V activity has been found to be elevated in experimental subarachnoid hemorrhage utilizing inhibition studies with the selective PDE V inhibitor, sildenafil. [3] Phosphodiesterase V inhibitors have been found to reduce cerebral vasospasm following experimental subarachnoid hemorrhage in a canine model. [3] Diomedi et al's finding [1] of sildenafil improving cerebrovascular reactivity to hypercapnia, probably through activating endothelial NO synthase, could indicate a mechanism which is inhibited in subarachnoid hemorrhage with increased PDE V activity causing impaired NO reactivity, resulting in cerebral vasospasm. References 1. Diomedi M, Sallustin f, Rizzato B et al. Sildenafil increases cerebrovascular resactivity: A transcranial Doppler study. Neurology. 2005; 65: 919-921. 2. Sobey C, Quan L. Impaired cerebral vasodilator responses of NO and PDE V inhibition after subarachnoid hemorrhage. Am J. Physiol. 1999; 277 (5 Pt 2): H1718-24. 3.Inoha S, Inamura T, Ikezaki K, et al. Type V phosphodiesterase expression in cerebral arteries with vasospasm after subarachnoid hemorrhage in a canine model. Neurol Res. 2002; 24: 607-12. Disclosure: The author reports no conflicts of interest.
Sildenafil may have potential for treatment of cerebral vasospasm in subarachnoid hemorrhage 16 January 2006
Marina Diomedi, Neuroscience Department - Policlinico Tor Vergata Viale Oxford, 81 - 00133 Rome Italy, Fabrizio Sallustio Send Correspondence to journal: Re: Sildenafil may have potential for treatment of cerebral vasospasm in subarachnoid hemorrhage Marina.Diomedi{at}uniroma2.it Marina Diomedi, et al.	We appreciate Dr. Brenner's thoughtful comments and agree that phosphodiesterase V (PDE-V) inhibitors could be useful for treatment of delayed arterial vasospasm induced by subarachnoid hemorrhage. According to previous sperimental studies, PDE V inhibitors could reduce cGMP hydrolysis rate resulting in an improvement of NO-mediated cerebral vasorelaxation, thus limiting vasoconstriction of major blood vessels. Moreover, the enhanced nitric oxide (NO) dependent vasodilatory response could potentiate collateral blood flow by means of an improved hemodynamic microvessels response in hypoperfused areas. We agree that more studies are needed to demonstrate PDE V inhibitors potential for treatment of long lasting vasospasm in humans in the light of the availability of molecules with long mean half-life such as Tadalafil. [4] Furthermore, focusing on the hemodynamic effect of other isoenzymes with different tissue distribution and functional significance should be of interest. [5] References 4. Porst H, Padma-Nathan H, Giuliano F, Anglin G, Varanese L, Rosen R. Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial. Urology 2003; 62:121-125. 5. Willette RN, Shiloh AO, Sauermelch CF, Sulpizio A, Michell MP, Cieslinski LB, Torphy TJ, Ohlstein EH. Identification, characterization, and functional role of phosphodiesterase type IV in cerebral vessels: effects of selective phosphodiesterase inhibitors. J Cereb Blood Flow Metab. 1997;17:210-219. The authors report no conflicts of interest.