Responsiveness of peripheral veins to transdermal and sublingual nitroglycerin in healthy male volunteers.

Nitroglycerin (NTG) is a potent vascular smooth muscle relaxant. With the widespread use of transdermal NTG patches for the prophylaxis of angina, two important issues have arisen: (a) the relative efficacy of transdermal NTG patches compared to other formulations of NTG, and (b) the possibility of development of tolerance to transdermal NTG. We have investigated these two issues by studying the effect of systemically administered NTG (transdermal patches, ointment, and sublingual tablets) on alpha-adrenergic receptor agonist-mediated constriction of human dorsal hand veins. Nitroglycerin patches and ointment (15-60 mg/24 h) applied for 1-4 h did not modify the sensitivity (ED50) to the alpha-adrenergic agonist, phenylephrine. However, sublingual NTG (0.15-0.60 mg) administration caused significant relaxation of partially constricted veins. Following exposure for 24 h to a NTG patch (15 mg/24 h), NTG dose-response curves were not altered suggesting there was no development of tolerance to transdermal NTG. We conclude from our observations that tolerance to transdermal NTG does not appear in veins, possibly due to the low plasma NTG concentrations produced by this preparation. Our results also indicate that high doses of transdermal NTG do not modify phenylephrine-mediated constriction of peripheral veins in humans.