Circulation, Vol 84, 2336-2345, Copyright © 1991 by American Heart Association
JD Parker, B Farrell, T Fenton, M Cohanim and JO Parker
BACKGROUND. Vasodilator therapy may be associated with reflex counter-
regulatory responses, and these responses may play a role in the
development of tolerance to nitroglycerin (GTN). METHODS AND RESULTS.
Standing systolic blood pressure, body weight, urinary sodium, and hormonal
responses to continuous (n = 10) and intermittent (n = 10) transdermal GTN
administration were studied in normal volunteers. There was rapid
attenuation of the hypotensive response to transdermal GTN therapy in the
continuous but not in the intermittent therapy group. Significant weight
gain and sodium retention occurred during continuous but not during
intermittent GTN therapy. This was accompanied by a greater decrease in
hematocrit in the continuous group, a finding that suggests that plasma
volume expansion occurred during continuous GTN therapy. Continuous GTN
therapy was associated with increases in plasma norepinephrine, atrial
natriuretic peptide, arginine, vasopressin, and plasma renin activity. A
different pattern of neurohormonal response was seen during intermittent
therapy, with values tending to return to baseline levels after the
nitrate-free interval. CONCLUSIONS. Continuous transdermal GTN therapy
leads to counter-regulatory responses associated with sodium retention and
probable plasma volume expansion. By contrast, intermittent transdermal GTN
therapy is associated with a different pattern of hormonal response, the
lack of sodium retention and no evidence of plasma volume expansion. It is
likely that these counter-regulatory responses play an important role in
the attenuation of nitrate effects.
ARTICLES
Counter-regulatory responses to continuous and intermittent therapy with nitroglycerin
Cardiovacular Division, Brigham and Women's Hospital, Boston, MA 02115.
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