Peripheral microvascular responses to norepinephrine in women with orthostatic intolerance

Abstract

We determined the effects of estradiol (E2) and progesterone (P4) on the cutaneous microvasculature during adrenergic (norepinephrine, NE) stimulation in eight orthostatic tolerant (OT) and eight intolerant (OI) women. We hypothesized that 1) OI have a blunted vasoconstrictor response to NE compared to OT; and 2) that female sex hormones modulate vasoconstriction. A cumulative stress index (CSI) during maximal lower body negative pressure determined orthostatic tolerance. Endogenous E2 and P4 was suppressed with daily administration of a GnRH antagonist (GnRH) for 16 days; we gave E2 (0.2 mg/day, patch) on days 4–16, and P4 (200 mg/day, pills) on days 13–16. We measured skin blood flow (laser Doppler flowmetry) during graded NE infusions (skin microdialysis) during GnRH, E2, and E2+P4. CSI was 871±86 and 397±65 for OT and OI respectively (P < 0.05). The vasoconstrictor response to NE during GnRH was similar between groups (log EC50: OT −3.9, CI −4.9 to −3.1; OI −4.4, CI −5.4 to −3.4). Combined E2+P4 enhanced the vasoconstrictor response in OT (EC50 −4.8, CI −5.6 to −4.1) but was reversed with Ketorolac (−3.8, −4.6 to −3.0). Hormones did not alter vasoconstriction in OI (EC50 −4.3, CI −5.0 to −3.7; −4.9, CI −5.5 to −4.4). Adrenergic response in skin microvasculature was similar between OT and OI. Although OI were insensitive to hormone treatments, P4 augments cutaneous adrenergic responses in OT. HL071159.