Continuous release of vasodilator prostanoids contributes to regulation of resting forearm blood flow in humans

Abstract

Continuous release of nitric oxide contributes to the maintenance of resting tone in the human forearm and coronary circulations; however, evidence for a similar role of vasodilator prostanoids such as prostacyclin is lacking. We examined whether continuous release of prostacyclin contributes to basal forearm blood flow. Flow was measured using venous occlusion plethysmography in 38 healthy volunteers [mean age 21.3 ± 2.5 yr (±SD); 13 female, 25 male] at rest, after administration of three incremental intra-arterial infusions of either the cyclooxygenase inhibitor aspirin or placebo, and before and after administration of the endothelium-dependent and -independent dilators acetylcholine (30 μg/min) and nitroprusside (1 μg/min). To assess the effect of aspirin on the production of prostacyclin, plasma 6-keto prostaglandin F1α(6-keto-PGF1α; the stable metabolite of prostacyclin) was measured by simultaneous arterial and venous sampling. Aspirin produced a time- and dose-dependent reduction in forearm blood flow, resulting in a 32% decrease at the highest dose. The effect was maximal after 10 min. Flow at rest and after aspirin doses of 1, 3, and 10 mg/min was 2.6 ± 0.2, 2.3 ± 0.2, 2.1 ± 0.2, and 1.8 ± 0.2 ml ⋅ 100 ml forearm tissue−1 ⋅ min−1, respectively (means ± SE, P< 0.001). Commensurate with these data, the net forearm production of 6-keto-PGF1α was 52.9 ± 16.4, 11.7 ± 8.6, 18.7 ± 8.5, and 12.0 ± 12.5 pg ⋅ 100 ml forearm tissue−1 ⋅ min−1 for the respective doses ( P = 0.04). No time-dependent reduction in flow was seen in subjects with vehicle infusion. Aspirin did not affect the responses to acetylcholine or nitroprusside. These data suggest that continuous release of prostacyclin plays a role in the maintenance of resting forearm blood flow. There appears to be a direct link between the reduction in flow with aspirin and inhibition of prostacyclin production.

Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation

“…Furthermore, there is no evidence of a dose-dependent release of vasoconstricting prostanoids. These results contrast with recent studies of the forearm macrocirculation in which basal release of vasoactive prostanoids has been shown to play a role in the maintenance of resting forearm blood flow in some (16) although not all studies (8,18,34).…”

ATP‐induced vasodilation in human skeletal muscle

“…Indomethacin-induced increase of FVR suggests that continuous release of prostacyclin plays a role in the maintenance of resting FBF. Wilson & Kapoor (1993) and Duffy et al (1998) previously detected that inhibition of cyclooxygenase with aspirin or indomethacin decreased the resting FBF by 20-30%. Prostacyclin also contributes to metabolic vasodilation (Kilbom & Wennmalm, 1976;Duffy et al, 1999a) as well as to resting and metabolic vasodilation in coronary arteries (Duffy et al, 1999b).…”

Linking erectile dysfunction and coronary artery disease

“…In normal physiologic conditions, PGI 2 exerts the predominate vascular effects. 26 Another endothelially released factor with variable vascular influences is angiotensin II. This peptide has vasoconstricting, prothrombotic, oxidant and atherogenic effects, as well as the ability to counteract these effects depending on the receptor (subtype AT1 or AT2) activated.…”