Effect of aspirin on vasodilation to bradykinin and substance P in patients with heart failure treated with ACE inhibitor.
OBJECTIVE
We wanted to examine some of the mechanisms by which aspirin might be responsible for counteraction of the effects of ACE inhibitors. Aspirin has been reported to counteract the effects of ACE inhibitors in patients with heart failure. Despite this, there is little evidence on what the mediator of such an effect might be, although there is some evidence to implicate bradykinin and, perhaps, substance P.


METHODS
Twelve patients with congestive heart failure treated with an ACE inhibitor were studied on two occasions, after abstaining from aspirin for 14 days, and after 14 days of aspirin 150 mg once daily. Forearm blood flow was measured by venous occlusion plethysmography during intrabrachial infusions of bradykinin and substance P, before and after intrabrachial aspirin.


RESULTS
Bradykinin caused profound vasodilation (peak 390%, 95% confidence intervals (CI) 300, 480%; P < 0.01), substance P slightly less (peak 222%, 95% CI 162, 283%; P < 0.01). Intra-brachial aspirin had no effect on its own. The response to bradykinin was unchanged by intrabrachial aspirin (peak 404%, 95% CI 304, 504%) or oral aspirin (peak 320%, 95% CI 209, 431%; P = 0.2). The response to substance P was unchanged by intrabrachial aspirin (peak 226%, 95% CI 171, 281%) or oral aspirin (peak 220%, 95% CI 142, 297%; P = 0.86).


CONCLUSIONS
Aspirin has no effect on the vasodilator response to bradykinin and substance P in patients with heart failure treated with an ACE inhibitor. Neither bradykinin nor substance P is likely to contribute to the reported interaction between aspirin and ACE inhibitors.
Davie
Andrew P
AP
Medical Research Council Clinical Research Initiative in Heart Failure, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK.
McMurray
John J V
JJ
D000368:Aged; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage*; D001920:Bradykinin / Q000494:pharmacology / Q000502:physiology*; D016001:Confidence Intervals; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013373:Substance P / Q000494:pharmacology / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D013373:Substance P; D001241:Aspirin; D001920:Bradykinin