title: Endothelin-1 limits increases in blood flow to native and collateral-dependent myocardium.
abstract: We hypothesized that blood flow to collateralized and noncollateralized myocardium is improved by antagonism of endothelin (ET) A receptors. Coronary collateral development was stimulated by placing an ameroid constrictor around the left circumflex coronary artery (LCx; collateralized region) in 11 swine. After 35 +/- 2 days, the left anterior descending coronary artery (LAD; noncollateralized region) was autoperfused at constant pressure using blood from a femoral artery. In group 1 (n = 6) transmural blood flow was measured using radioactive microspheres in the LAD, LCx, and border regions (i.e., area between LAD and LCx) during pacing stress while vehicle (phosphate-buffered saline) was infused into the LAD coronary artery (pace 1). Approximately 55 min later, a second period of pacing (pace 2) was performed in the presence of ETA receptor antagonism (BQ-123; 5 mg.ml-1.min-1 ic). In the time control group (group 2, n = 5) vehicle was infused during both pacing periods. Indexes of myocardial oxygen demand were similar between paces 1 and 2 in each group. Compared with the first pacing period, transmural blood flow (ml.100 g-1.min-1) was higher (P < 0.05) during ETA receptor antagonism (i.e., pace 2) in the LAD (105 +/- 8 vs. 139 +/- 9), border (51 +/- 5 vs. 83 +/- 7), and LCx regions (22 +/- 3 vs. 41 +/- 4, respectively) in group 1. In group 2, while perfusion in the border (98 +/- 17 vs. 103 +/- 16) and LCx regions (19 +/- 4 vs. 27 +/- 6) was similar in paces 1 and 2, LAD transmural flow was greater (134 +/- 9 vs. 160 +/- 13; P < 0.05) during the second pacing period. However, the percent increase in LAD flow comparing pace 1 with 2 was greater (P < 0.05) in group 1 (39 +/- 6%) compared with group 2 (20 +/- 7%). These data suggest that during the stress of pacing blood flow to collateralized and noncollateralized myocardium is improved in the presence of ETA receptor blockade.
authors.affiliation: Department of Internal Medicine, University of California-Davis 95616, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Symons
authors.forename: S V
authors.initials: SV
authors.lastname: Rendig
authors.forename: L W
authors.initials: LW
authors.lastname: Fu
authors.forename: J C
authors.initials: JC
authors.lastname: Longhurst
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure; D003097:Collateral Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000502:physiology*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D005112:Extracorporeal Circulation / Q000295:instrumentation / Q000379:methods; D005263:Femoral Artery / Q000502:physiology; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D008863:Microspheres; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology*; D013552:Swine
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin