Even low-dose aspirin inhibits arachidonic acid-induced vasodilation in heart failure.
BACKGROUND
There is some evidence that aspirin may be harmful to patients with congestive heart failure treated with angiotensin-converting enzyme (ACE) inhibitors, but there has never been any direct examination of the vascular effects of aspirin in these patients. We sought to determine whether there is an arachidonic acid-dependent vasodilator pathway in resistance arteries in humans, whether it is affected by congestive heart failure, and whether it is inhibited by low-dose aspirin.


METHODS
A locally active dose of arachidonic acid was infused into the nondominant brachial artery while forearm blood flow was measured by venous occlusion plethysmography in 10 healthy subjects in a control group and 15 patients with congestive heart failure treated with ACE inhibitor. Patients with congestive heart failure were studied after administration of 0 mg, 75 mg, and 300 mg aspirin for 14 days.


RESULTS
Arachidonic acid produced progressive and incremental vasodilation (up to 64%). There was no significant difference between patients and healthy control subjects studied after administration of 0 mg aspirin. In patients, however, administration of 75 mg and 300 mg aspirin inhibited mean vasodilation by 55% and 59%, respectively.


CONCLUSIONS
There is an arachidonic acid-dependent vasodilator pathway in humans. This pathway is not significantly affected by congestive heart failure. It is significantly inhibited by even low-dose aspirin therapy. These results imply that even the very lowest dose of aspirin in common use for cardioprotection has potentially detrimental vasoconstrictor effects.
Davie
A P
AP
Medical Research Council Clinical Research Initiative in Heart Failure, University of Glasgow, Scotland.
Love
M P
MP
McMurray
J J
JJ
D000328:Adult; D000368:Aged; D016718:Arachidonic Acid; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001916:Brachial Artery / Q000187:drug effects; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D010991:Plethysmography; D014664:Vasodilation / Q000187:drug effects*
D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D001241:Aspirin