Author + information
- Received June 15, 1992
- Revision received October 28, 1992
- Accepted October 29, 1992
- Published online May 1, 1993.
- ↵†Present address and address for correspondence: John D. Parker, MD, Division of Cardiology, Mount Sinai Hospital, Suite 1609, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5.
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 trassdermal 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 uitrate effects during sustained therapy. That therapy with an angiotensin-coverting 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.
↵1 Dr. John D. Parker is a Scholar of the Medical Research Council of Canada, Ottawa, Ontario.
☆ This study was supported by Clinical Research Center Grant MOIRR02635 from the National Institutes of Health, Bethesda, Maryland and by a grant from the Ciba-Geigy Corporation, Summit, New Jersey.
- Received June 15, 1992.
- Revision received October 28, 1992.
- Accepted October 29, 1992.