Effect of therapy with an angiotensin-converting enzyme inhibitor on hemodynamic and counterregulatory responses during continuous therapy with nitroglycerin

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

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.

This article has been cited by other articles:

				N. Hirai, H. Kawano, H. Yasue, H. Shimomura, S. Miyamoto, H. Soejima, I. Kajiwara, T. Sakamoto, M. Yoshimura, H. Nakamura, et al. Attenuation of Nitrate Tolerance and Oxidative Stress by an Angiotensin II Receptor Blocker in Patients With Coronary Spastic Angina Circulation, September 23, 2003; 108(12): 1446 - 1450. [Abstract] [Full Text] [PDF]

				T. Gori and J. D. Parker The Puzzle of Nitrate Tolerance: Pieces Smaller Than We Thought? Circulation, October 29, 2002; 106(18): 2404 - 2408. [Full Text] [PDF]

				H. Watanabe, M. Kakihana, S. Ohtsuka, and Y. Sugishita Preventive effects of carvedilol on nitrate tolerance--a randomized, double-blind, placebo-controlled comparative study between carvedilol and arotinolol J. Am. Coll. Cardiol., November 1, 1998; 32(5): 1201 - 1206. [Abstract] [Full Text] [PDF]

				J. Zanzinger, J. Czachurski, and H. Seller Impaired Modulation of Sympathetic Excitability by Nitric Oxide After Long-term Administration of Organic Nitrates in Pigs Circulation, June 16, 1998; 97(23): 2352 - 2358. [Abstract] [Full Text] [PDF]

				H. Watanabe, M. Kakihana, S. Ohtsuka, and Y. Sugishita Randomized, Double-Blind, Placebo-Controlled Study of Ascorbate on the Preventive Effect of Nitrate Tolerance in Patients With Congestive Heart Failure Circulation, March 10, 1998; 97(9): 886 - 891. [Abstract] [Full Text] [PDF]

				H. Watanabe, M. Kakihana, S. Ohtsuka, and Y. Sugishita Randomized, Double-Blind, Placebo-Controlled Study of Supplemental Vitamin E on Attenuation of the Development of Nitrate Tolerance Circulation, October 21, 1997; 96(8): 2545 - 2550. [Abstract] [Full Text]

				J. D. Parker, A. B. Parker, B. Farrell, and J. O. Parker The Effect of Hydralazine on the Development of Tolerance to Continuous Nitroglycerin J. Pharmacol. Exp. Ther., February 1, 1997; 280(2): 866 - 875. [Abstract] [Full Text]

				J. D. Parker, A. B. Parker, B. Farrell, and J. O. Parker Effects of Diuretic Therapy on the Development of Tolerance to Nitroglycerin and Exercise Capacity in Patients With Chronic Stable Angina Circulation, February 15, 1996; 93(4): 691 - 696. [Abstract] [Full Text]

				J. D. Parker, A. B. Parker, B. Farrell, and J. O. Parker Intermittent Transdermal Nitroglycerin Therapy : Decreased Anginal Threshold During the Nitrate-Free Interval Circulation, February 15, 1995; 91(4): 973 - 978. [Abstract] [Full Text]