Local infusion of arachidonic acid produced dose-dependent venodilatation that was abolished by a high dose of aspirin (1 g) but not a low dose (75 mg).
Does local infusion of arachidonic acid alter vascular tone in healthy volunteers, and is this effect modulated by different doses of aspirin?
Local generation of prostanoids in human vessels in vivo alters vascular tone, and this synthesis is blocked by anti-inflammatory (1 g) but not cardioprotective (75 mg) doses of aspirin.
BACKGROUND: Human endothelial and vascular smooth muscle cells synthesize prostanoids. Several of these have been implicated in the physiological and pathophysiological regulation of vascular tone; however, there is no direct evidence that human blood vessels synthesize sufficient prostanoid to alter vessel tone. METHODS AND RESULTS: We explored the effects of local infusions of arachidonic acid on the tone of preconstricted superficial hand veins in healthy volunteers. Aspirin was used to assess the contribution of prostanoids to the responses seen. Local infusion of arachidonic acid produced a dose-dependent dilatation of preconstricted veins. This was abolished by local infusion of aspirin. Oral aspirin was also effective: a high (anti-inflammatory) dose of aspirin (1 g) taken 2 hours before the experiment blocked the arachidonic acid-induced venodilatation; however, a low (cardioprotective) dose of aspirin (75 mg) did not. Unlike the responses to arachidonic acid, responses to glyceryltrinitrate and bradykinin were unaltered by aspirin (1 g). Ex vivo platelet aggregation was inhibited by aspirin in both high and low doses. Aspirin (1 g) inhibited arachidonic acid-induced venodilatation for up to 5 days. The time course was similar for vascular and platelet effects. CONCLUSIONS: The present findings demonstrate that local generation of prostanoids in a human vessel in vivo alters vascular tone. The predominant prostanoid synthesized is a dilator and its synthesis can be blocked by an anti-inflammatory but not a cardioprotective dose of aspirin. The results suggest that selective inhibition of platelet aggregation by oral aspirin might be a function of dose rather than the interval between doses.
Bhagat et al. (Sun,) conducted a other in Healthy volunteers. Arachidonic acid infusion and aspirin was evaluated on Venodilatation of preconstricted superficial hand veins. Local infusion of arachidonic acid produced dose-dependent venodilatation that was abolished by a high dose of aspirin (1 g) but not a low dose (75 mg).