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

Response to Khaodhiar and Veves

From the Department of Medicine, Division of Endocrinology, Tulane University Medical Center, New Orleans, Louisiana

We appreciate the comments of Drs. Khaodhiar and Veves (1). We agree that in order to dissect the action of sildenafil on the endothelial cell and the vascular smooth muscle cell it is necessary to perform measurements that evaluate both endothelium-dependent and endothelium-independent vasodilatation. However, the latter requires the use of nitrates, which have the potential for serious (and potentially fatal) hypotension when used concomitantly with sildenafil. When giving us an investigational new drug exemption to carry out this study, the Food and Drug Administration specifically asked us not to use nitrates. Nevertheless, our results clearly demonstrate a beneficial effect of sildenafil on vascular reactivity that lasts well beyond the time expected from pharmacokinetic studies of the drug (2). Such treatment is thus able to overcome what is well recognized as a defect in endothelial function—even if possibly mediated through actions on smooth muscle cells.

We note that Dishy et al. (3) have demonstrated that sildenafil administration increased sensitivity to local nitroglycerin. However, their studies were carried out in healthy volunteers, whereas we studied patients with diabetes who may have had asymptomatic coronary artery disease. Much as we would like to do the study as suggested by Khaodhiar and Veves, our overriding concern is for patient safety (as it should be in all clinical research).

Footnotes

Address correspondence to Vivian Fonseca, Tulane University Medical Center, Division of Endocrinology, Department of Medicine, 1430 Tulane Ave. (SL 53), New Orleans, LA 70112. E-mail: vfonseca{at}tulane.edu.

References

1. Khaodhiar L, Veves A: Acute and prolonged effects of sildenafil on brachial artery flow-mediated dilatation in type 2 diabetes (Letter). Diabetes Care 26:962–963, 2003[Free Full Text]
   
2. 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]
   
3. 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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