title: Acute effects of 17 beta-estradiol on the coronary microcirculation: observations in sedated, closed-chest domestic swine.
abstract: OBJECTIVE
  To test the hypotheses: that acute administration of 17 beta-estradiol dilates normal coronary microvessels in vivo; that coronary microvascular responses to acute estrogen stimulation exhibit sexual dimorphism; and that nitric oxide has a role in mediating these effects.
  
  
  METHODS
  Measurements of hemodynamics, coronary flow velocity (Doppler), myocardial blood flow (microspheres) and oxygen consumption were made in closed-chest swine: group 1 consisted of castrated juvenile males, groups 2 and 3 of estrogen pretreated, castrated juvenile males, and group 4 of sexually mature females. 17 beta-Estradiol (2, 20 or 200 ng/kg) was given by intracoronary injection and data obtained 20-30 min later; additional measurements were made 1 h after the 200 ng/kg dose. The effect of L-NG-monomethylarginine (L-NMMA) on 17 beta-estradiol responses was also tested. Tissue and blood concentrations of 17 beta-estradiol, and concentrations of estrogen receptor in myocardium and coronary vessels were obtained.
  
  
  RESULTS
  In estrogen-naive castrated males, 17 beta-estradiol had no effect on coronary flow velocity or myocardial blood flow, but 1 h after the 200 ng/kg dose there was an increase in diastolic coronary resistance compared with baseline (48 +/- 20 versus 41 +/- 17 mmHg/mkHz; P < 0.05). Estrogen pretreated castrated males also showed no change in myocardial blood flow after 17 beta-estradiol, but coronary flow velocity decreased (P < 0.05) compared with baseline 1 h after the 200 ng/kg dose (from 1.69 +/- 0.61 to 1.41 +/- 0.42 kHz) and diastolic coronary resistance increased significantly (P < 0.01) compared with control at this time (51 +/- 15 compared with 39 +/- 14 mmHg/mkHz). In sexually mature females, 17 beta-estradiol had no effect on myocardial blood flow but did cause a significant (P < 0.05) decrease in diastolic coronary vascular resistance compared with baseline (51 +/- 9 mmHg/mkHz) at both the 20 ng/kg and the 200 ng/kg doses (both 43 +/- 11 mmHg/mkHz). Coronary flow velocity also increased (P < 0.06) compared with baseline (1.34 +/- 0.26 mmHg/mkHz) after the 200 ng/kg dose (1.69 +/- 0.61 mmHg/mkHz). L-NMMA had no effect on flow responses to 17 beta-estradiol in any group. Classical estrogen receptors were not present in myocardium or coronary arteries from male or female swine.
  
  
  CONCLUSIONS
  These results demonstrate that 17 beta-estradiol exerts a mild constrictor effect on the coronary microvessels of normal castrated, juvenile males whether estrogen-naive or estrogen-pretreated. In contrast, sexually mature normal females exhibit mild dilatation of the coronary microcirculation in response to acute estrogen stimulation. Nitric oxide does not appear to have a role in mediating the dilator response in females, and classical estrogen receptors are not involved. A direct membrane effect of the hormone (perhaps via alteration in potassium conductance) seems likely, and demonstrates sexual dimorphism.
authors.affiliation: Department of Medicine, Rhode Island Hospital, Providence, USA.
authors.forename: M
authors.initials: M
authors.lastname: Berman
authors.forename: H
authors.initials: H
authors.lastname: Gewirtz
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D016292:Procedural Sedation; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007261:Infusions, Intra-Arterial; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D009919:Orchiectomy; D010101:Oxygen Consumption; D011960:Receptors, Estrogen / Q000378:metabolism; D012727:Sex Characteristics; D013552:Swine; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011960:Receptors, Estrogen; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004958:Estradiol