Neurohormonal activation during nitrate therapy: a possible mechanism for tolerance.
The hemodynamic and antianginal effects of the organic nitrates are greatly reduced during therapy designed to provide 24-hour protection throughout each day. Although the mechanisms of tolerance are not clearly understood, it is likely that tolerance is related to a combination of reduced sulfhydryl groups in vascular smooth muscle and neurohormonal activation. These changes would reduce nitrate-induced vasodilation and induce sodium and water retention with an increase in plasma volume. These reflex neurohormonal changes would reduce the hemodynamic effect of any given degree of nitrate-induced vasodilation. Although preliminary studies suggest that diuretic therapy or the use of converting enzyme inhibitors may reduce or abolish tolerance, further clinical studies are required to confirm these findings.
Parker
J O
JO
Department of Medicine, Queen's University, Kingston, Ontario, Canada.
Parker
J D
JD
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D004232:Diuretics / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D006439:Hemodynamics / Q000187:drug effects*; D006728:Hormones / Q000097:blood; D006801:Humans; D005996:Nitroglycerin / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D006728:Hormones; D005996:Nitroglycerin