Counter-regulatory responses to continuous and intermittent therapy with nitroglycerin

Area of Science:

• Cardiovascular Pharmacology
• Endocrinology

Background:

• Vasodilator therapy, including nitroglycerin (GTN), can trigger reflex counter-regulatory responses.
• These responses may contribute to the development of tolerance to GTN's effects.

Purpose of the Study:

• To compare the counter-regulatory responses to continuous versus intermittent transdermal nitroglycerin (GTN) administration.
• To investigate the role of these responses in nitroglycerin tolerance.

Main Methods:

• Normal volunteers received continuous or intermittent transdermal GTN.
• Measurements included blood pressure, body weight, urinary sodium, hematocrit, and plasma hormone levels (norepinephrine, atrial natriuretic peptide, arginine vasopressin, renin activity).

Main Results:

• Continuous GTN led to rapid attenuation of hypotensive response, weight gain, sodium retention, and plasma volume expansion.
• Intermittent GTN did not show significant weight gain or sodium retention, with hormonal responses returning to baseline.
• Continuous therapy increased plasma norepinephrine, atrial natriuretic peptide, arginine vasopressin, and plasma renin activity.

Conclusions:

• Continuous transdermal GTN therapy induces counter-regulatory responses, including sodium retention and probable plasma volume expansion.
• Intermittent transdermal GTN therapy results in a different hormonal pattern without sodium retention or plasma volume expansion.
• These counter-regulatory mechanisms are likely key to the attenuation of nitrate effects, suggesting intermittent therapy may mitigate tolerance.