title: Mechanisms responsible for endothelial dysfunction associated with acute estrogen deprivation in normotensive women.
abstract: BACKGROUND
  The goal of this study was to evaluate whether endothelial dysfunction associated with acute estrogen deprivation is caused by an alteration in the L-arginine-nitric oxide (NO) pathway and oxidative stress. Methods and Results-In 26 healthy women (age, 45.7+/-5.4 years) and 18 fertile women with leiomyoma (age, 44.5+/-5.1 years), we studied forearm blood flow (strain-gauge plethysmography) changes induced by intrabrachial acetylcholine (0. 15, 0.45, 1.5, 4.5, or 15 microgram. 100 mL(-1). min(-1)) or sodium nitroprusside (1, 2, or 4 microgram. 100 mL(-1). min(-1)), an endothelium-dependent or -independent vasodilator, respectively. The NO pathway was evaluated by repeating acetylcholine during L-arginine (200 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients) or N(G)-monomethyl-L-arginine (L-NMMA; 100 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients); production of cyclooxygenase-derived vasoconstrictors was assessed by repeating acetylcholine during indomethacin (50 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients) or vitamin C (8 mg. 100 mL(-1). min(-1); 13 control subjects and 9 patients). Patients repeated the study within 1 month after ovariectomy and again after 3 months of estrogen replacement therapy (ERT; 17 beta-estradiol TTS, 50 microgram/d). Basally, vasodilation to acetylcholine was potentiated and inhibited by L-arginine and L-NMMA, respectively (P<0.05), but was unaffected by indomethacin or vitamin C. After ovariectomy, the modulating effect of L-arginine and L-NMMA disappeared, whereas indomethacin and vitamin C potentiated the response to acetylcholine (P<0.05). ERT restored L-arginine and L-NMMA effects on vasodilation to acetylcholine but prevented the potentiation caused by indomethacin or vitamin C. Response to sodium nitroprusside was unaffected by either ovariectomy or ERT.
  
  
  CONCLUSIONS
  Endothelial dysfunction secondary to acute endogenous estrogen deprivation is caused by reduced NO availability. Cyclooxygenase-dependent production of oxidative stress could be responsible for this alteration.
authors.affiliation: Department of Internal Medicine, University of Pisa, Udine, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Virdis
authors.forename: L
authors.initials: L
authors.lastname: Ghiadoni
authors.forename: S
authors.initials: S
authors.lastname: Pinto
authors.forename: M
authors.initials: M
authors.lastname: Lombardo
authors.forename: F
authors.initials: F
authors.lastname: Petraglia
authors.forename: A
authors.initials: A
authors.lastname: Gennazzani
authors.forename: S
authors.initials: S
authors.lastname: Buralli
authors.forename: S
authors.initials: S
authors.lastname: Taddei
authors.forename: A
authors.initials: A
authors.lastname: Salvetti
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007889:Leiomyoma / Q000503:physiopathology; D008875:Middle Aged; D010052:Ovariectomy; D011184:Postoperative Period; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D014594:Uterine Neoplasms / Q000503:physiopathology; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D004967:Estrogens; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D001120:Arginine; D000109:Acetylcholine; D001205:Ascorbic Acid; D007213:Indomethacin