Vasomotor effects and pathophysiologic relevance of F₂-isoprostane formation in vascular diseases

We read with the utmost interest the study by Iuliano et al. (1). The investigators showed for the first time that concentrations of 2-F₂-isoprostane regioisomers, iPF_2α-III (15-F_2t-IsoP) and iPF_2α-VI (5-F_2t-IsoP), were markedly increased in the coronary sinus following percutaneous transluminal coronary angioplasty (PTCA). In their study, the levels of iPF_2α-III in the coronary sinus after angioplasty, measured by GC/NICI-MS, were 125 pg/ml, which is equivalent to 0.35 nmol/l. Such levels are in the same range as plasma samples in nonsmokers (0.103 nmol/l [2], in ruptured aortic aneurysm 0.436 nmol/l [3]) and umbilical cord arterial samples in newborns (0.898 nmol/l [4]), although caution should be taken when comparing these results as the methodology used to measure iPF_2α-III was different. Such data do not support the conclusion that these concentrations are similar to the EC₅₀values observed with iPF_2α-III on porcine and bovine coronary arteries that are in the micromolar range (5). Indeed, the potency of iPF_2α-III was in the micromolar range in most studies performed on conductance vessels, including coronary arteries (6), although data on human coronary arteries are lacking.

Consequently, the concentrations observed in this study (1)are unlikely to induce a vasoactive effect in conductance vessels. In contrast, the potency of iPF_2α-III in the microcirculation is higher, and in some studies close to the nanomolar range (6). As a consequence, whereas the concentrations reported in the Iuliano et al. study (1)are unlikely to contribute to epicardial coronary artery vasoconstriction, local concentrations may be sufficiently high to induce intramyocardial artery vasoconstriction. Further in vivo and in vitro studies are required to determine whether isoprostanes might contribute to vasoconstriction in vascular diseases.

• American College of Cardiology