Changes in endothelium-dependent vasodilatation and alpha-adrenergic responses in resistance vessels during the menstrual cycle in healthy women

During the menstrual cycle, changes in endothelium-dependent vasodilatation have been demonstrated in conduit vessels in vivo, but responses in resist ance vessels have not been studied. The aim of this study was to examine en dothelium-dependent vasodilatation, the effects of local nitric oxide synth esis, and alpha -adrenergic constriction in resistance vessels during the m enstrual cycle in 15 healthy female volunteers (mean age, 28.07 +/- 2.1 yr) . Forearm blood flow in response to intrabrachial infusion of bradykinin (1 0, 30, and 100 pmol/min; endothelium-dependent vasodilator), glyceryl trini trate (4, 8, and 16 nmol/min; endothelium-independent vasodilator), noradre naline (60, 120, and 240 pmol/min; alpha -adrenergic receptor agonist), and N-G-monomethyl-L-arginine (1, 2, and 4 mu mol/min; nitric oxide synthase i nhibitor) was assessed by venous occlusion plethysmography. All subjects we re studied in early menstrual phase (days 1-4) and midcycle (days 10-13). V asodilator response to bradykinin, expressed as the within-subject mean dif ference in the area under the dose-response curve between phases, was signi ficantly increased at midcycle compared with that in the early menstrual ph ase (486.5 +/- 165.0; P = 0.01), whereas there was no significant differenc e in response to glyceryl trinitrate (185.8 +/- 239.0; P = 0.45). The vasoc onstrictor response to noradrenaline was significantly greater at midcycle (97.1 +/- 39.4; P = 0.027), but the response to N-G-monomethyl-L-arginine w as not significantly different (17.5 +/- 35.2; P = 0.63). Serum estradiol w as approximately 3-fold higher at midcycle, with a mean difference of 252.3 +/- 56.0 pmol/L (P = 0.0005). Progesterone concentrations were not signifi cantly different (-0.11 +/- 0.1 nmol/L; P = 0.28). Differences in endogenou s estrogen levels between menstrual phases may underlie changes in bradykin in and noradrenaline responses. If exogenous estrogens have similar effects , the balance of these two opposing actions may determine whether estrogen replacement in postmenopausal women has beneficial or harmful effects on th e vasculature.