Objectives: We sought to characterize the reflex counterregulatory responses throughout a 6-day period of continuous nitroglycerin therapy and to examine the effect of concurrent administration of a non-thiol angiotensin-converting enzyme inhibitor (benazepril) on the nature of those responses.
Background: Therapy with nitroglycerin has been shown to be associated with reflex counterregulatory responses.
Methods: Standing systolic blood pressure, hormonal responses, urinary sodium and hematocrit levels were monitored during 6 days of continuous transdermal nitroglycerin therapy in normal volunteers. Using a double-blind randomized parallel design, 11 subjects received placebo and 9 received benazepril. Hemodynamic responses to sublingual nitroglycerin administration were evaluated before and after sustained therapy with transdermal nitroglycerin.
Results: Attenuation of the hypotensive response to transdermal nitroglycerin was rapid in the group receiving placebo and the group receiving benazepril. There were no significant hormonal responses to transdermal nitroglycerin in either group, and sodium retention was modest and transient. Hematocrit levels decreased after transdermal nitroglycerin therapy and remained depressed for the duration of nitroglycerin therapy, a finding that suggests plasma volume expansion. Blood pressure responses to sublingual nitroglycerin in both groups were similar before and after continuous transdermal nitroglycerin therapy.
Conclusions: These data suggest that plasma volume expansion plays a more important role than neurohormonal responses in the loss of nitrate effects during sustained therapy. That therapy with an angiotensin-converting enzyme inhibitor did not modify the hemodynamic responses to continuous nitroglycerin therapy supports this conclusion. Further investigation will be necessary to confirm whether therapy with an angiotensin-converting enzyme inhibitor has any role in the prevention of nitrate tolerance.