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(Circulation. 1995;92:2113-2118.)
© 1995 American Heart Association, Inc.

Articles

Vasodilatation to Arachidonic Acid in Humans

An Insight Into Endogenous Prostanoids and Effects of Aspirin

Kiran Bhagat, BSc, MRCP; Joe Collier, MA, MD, FRCP; Patrick Vallance, BSc, MD, FRCP

From the Clinical Pharmacology Unit, Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, London, UK.

Correspondence to Dr Bhagat, Clinical Pharmacology Unit, Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, London SW17 ORE, UK.

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.

Key Words: vasodilation • aspirin

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