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Acute and Prolonged Effects of Sildenafil on Brachial Artery Flow-Mediated Dilatation in Type 2 Diabetes

From the Joslin-Beth Israel Deaconess Foot Center, Microcirculation Lab, Department of Surgery, Boston, Massachusettes

In a recent article by Desouza et al. (1), an improvement of brachial artery flow-mediated vasodilatation, a measurement indicating endothelium-dependent vasodilation, was reported with both acute and prolonged sildenafil treatment. No measurements of endothelium-independent vasodilation were performed. As the administration of sublingual nitroglycerin is mainly used to evaluate endothelium-independent vasodilation, it is understandable that possible side effects related to the concomitant use of sildenafil and nitroglycerine were the main reason for omitting this measurement. However, we believe that although the presented data are very interesting, they do not support the main conclusion of the article, namely that sildenafil improves endothelial function.

Sildenafil is a type-5 phosphodiesterase inhibitor that works directly at the vascular smooth muscle cell by preventing a breakdown of cyclic guanosine monophosphate (cGMP). Therefore, it should not affect the nitric oxide production and release by vascular endothelial cell, but it should enhance its action on the smooth muscle cell as it prolongs the action of the cGMP that is generated by the action of the nitric oxide.

The only way to dissect the action of sildenafil on the endothelial cell and the vascular smooth muscle cell is to perform measurements that evaluate both the endothelium-dependent and -independent vasodilation. In case the endothelium-dependent vasodilation improves while the endothelium-independent remains unchanged, a claim can be made that sildenafil affects the endothelial function. However, in case there is also an improvement in the endothelium-independent vasodilation. Therefore, we believe that the data should be interpreted as indicating a direct action of sildenafil on the smooth muscle cell, while an additional effect on the endothelial cell cannot be excluded. In case a disproportional improvement in the endothelium-independent measurement is noticed, it can be reasonably concluded that sildenafil mainly affects the smooth cell function. It should also be noted that such data have been provided in a previous study of healthy men (2). In that study, sildenafil administration increased sensitivity to local nitroglycerin (endothelial-independent vasodilatation) in the subjects’ hand vein, resulting in the decrease in a 50% effective dose by about fourfold. In contrast, sildenafil did not significantly affect the maximal venodilatory response to acetylcholine or flow mediated artery vasodilatation (endothelial-dependent vasodilatation).

In conclusion, we believe that the data by Desouza et al. (1) provide significant information regarding the effect of sildenafil on the vasculature, but the conclusions should be modified to state that sildenafil improves vascular reactivity (which encompasses both endothelium-dependent and -independent vasodilation).

Footnotes

Address correspondence to Lalita Khaodhiar, MD, Joslin-Beth Israel Deaconess Foot Center, Microcirculation Lab, Department of Surgery, 1 Deaconess Rd., Palmer 317, Boston, MA 02215. E-mail: lkhaodhi{at}caregroup.harvard.edu.

References

1. Desouza C, Parulkar A, Lumpkin D, Akers D, Fonseca V: Acute and prolonged effects of sildenafil on brachial artery flow-mediated dilatation in type 2 diabetes. Diabetes Care 25:1336–1339, 2002[Abstract/Free Full Text]
   
2. Dishy V, Sofowora G, Harris PA, Kandcer M, Zhan F, Wood AJ, Stein CM: The effect of sildenafil on nitric oxide-mediated vasodilation in healthy men. Clin Pharmacol Ther 70:270–279, 2001[Medline]
   

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				V. Fonseca Acute and Prolonged Effects of Sildenafil on Brachial Artery Flow-Mediated Dilatation in Type 2 Diabetes: Response to Khaodhiar and Veves Diabetes Care, March 1, 2003; 26(3): 963 - 963. [Full Text] [PDF]

This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Khaodhiar, L. Articles by Veves, A. Search for Related Content PubMed PubMed Citation Articles by Khaodhiar, L. Articles by Veves, A. Social Bookmarking                What's this?