Preventive effects of angiotensin-converting enzyme inhibitors on nitrate tolerance during continuous transdermal application of nitroglycerin in patients with chronic heart failure.

Abstract

This study was designed to investigate the effect of angiotensin-converting enzyme (ACE) inhibitors with and without a sulfhydryl group on intracellular production of cGMP, forearm blood flow, and neurohormonal factors during continuous transdermal application of nitroglycerin in patients with chronic heart failure. Platelet cGMP level and forearm blood flow were measured before and 5 min after sublingual administration of nitroglycerin (NTG) in 20 patients with chronic heart failure during the following 4 phases: (1) baseline phase; (2) NTG phase (1 week after NTG tape 10 mg/day); (3) CPT phase (1 week after both captopril 37.5 mg/day and NTG tape 10 mg/day); and (4) ENL phase (1 week after both enalapril 5 mg/day and NTG tape 10 mg/day). The platelet GMP level before sublingual NTG and forearm blood flow were significantly higher during the 3 phases with NTG tape than during the control phase. The percent increases in platelet cGMP level and forearm blood flow after sublingual NTG were significantly lower during the NTG phase than during the baseline phase. In contrast, concomitant application of ACE inhibitors maintained the percent increase in platelet cGMP level and forearm blood flow. These results indicate that concomitant therapy with ACE inhibitors may be helpful in preventing the attenuation of intracellular cGMP production in patients with chronic heart failure during continuous transdermal application of NTG.