Venous responsiveness to norepinephrine in healthy subjects: effects of single doses of 325 mg aspirin.
BACKGROUND
Antithrombotic doses of aspirin, which are widely used in patients with cardiovascular disease, may inhibit prostaglandin synthesis but the physiologic significance with regard to vascular tone is not well defined. We hypothesized that inhibition of vasodilator prostaglandin synthesis by aspirin would significantly increase sympathetic-mediated venoconstriction.


METHODS
Twelve healthy volunteers (mean age, 24.5 +/- 0.8 years; age range, 19 to 30 years) were studied on two mornings approximately 7 days apart and not less than 90 minutes after a randomized single dose of 325 mg aspirin or matching placebo. Distension of dorsal hand veins was measured with use of the linear variable differential transformer technique during local infusions of exogenous norepinephrine (0.125 to 1,024 ng/min) and during release of endogenous norepinephrine from sympathetic activation by a forehead cold pressor test. Hemodynamic parameters and venous plasma catecholamine levels were measured. Antiplatelet activity of the dose of aspirin was confirmed in three subjects.


RESULTS
Aspirin increased venoconstriction to norepinephrine, causing a significant shift to the left (P < .03) of the norepinephrine dose-response curve and a significant decrease in logED50 (P < .03), representing a decrease in the dose of norepinephrine required to reduce vein distension by 50% from 50 to 25 ng/min. Venoconstriction to the cold pressor test was significantly increased by aspirin (10% +/- 3% versus 3% +/- 1% for placebo; P < .02). Cold pressor-induced increases in mean arterial pressure were significantly larger with aspirin compared with placebo (18 +/- 1 versus 14 +/- 1 mm Hg, respectively; P < .03). Baseline levels and stress-induced increases in plasma norepinephrine were not different between days.


CONCLUSIONS
The results suggest that aspirin inhibits the role of vasodilator prostaglandins in modulating peripheral venoconstriction and increases vascular resistance during physiologic stress in young healthy subjects.
Dzeka
T N
TN
Department of Medicine, University of Western Ontario, and the London Health Sciences Center, Canada.
Kuzminski
P
P
Arnold
J M
JM
D000328:Adult; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology*; D003080:Cold Temperature; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D011453:Prostaglandins / Q000096:biosynthesis*; D012016:Reference Values; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014680:Veins
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D001241:Aspirin; D009638:Norepinephrine