title: Endothelium-dependent regulation of the ophthalmic microcirculation in the perfused porcine eye: role of nitric oxide and endothelins.
abstract: OBJECTIVE
  The endothelium produces nitric oxide and endothelin (ET). This study was designed to investigate the endothelium-dependent regulation of the porcine ophthalmic microcirculation.
  
  
  METHODS
  Isolated porcine eyes were perfused with a modified Langendorff setup (Hugo Sachs Elektronik KG, Freiburg, Germany) at a perfusion pressure of 80 cm H2O with Krebs-Ringer bicarbonate solution (37 degrees C; 95% O2, 5% CO2).
  
  
  RESULTS
  The inhibitor of nitric oxide formation, L-nitroarginine methylester (L-NAME; 10(-6) to 10(-4) M), evoked decreases in flow (maximal decrease, 39% +/- 6%; P < 0.005 versus control). The endothelium-dependent vasodilator bradykinin evoked increases in ophthalmic flow (maximal increase, 26% +/- 2%; P < 0.05 versus control) prevented by L-NAME. The effect of endothelin-1 (ET-1; 10(-12) to 10(-11) M) on flow was biphasic, with early vasodilation (1 to 2 minutes) and late vasoconstriction. At 10(-12) M, the increase in flow was most pronounced (24% +/- 5%; P < 0.05 versus control), whereas 10(-10) M caused only significant decreases in flow (59% +/- 5%; P < 0.001 versus control). Endothelin-3 (ET-3) evoked similar vasodilator effects as ET-1 but less vasoconstriction. The vasodilator effects of ET-3 were prevented by pretreatment of the eye with indomethacin (10(-5) M, to block the production of prostaglandins; P < 0.05 versus control). The endothelinA receptor antagonist FR-139317 significantly reduced vasoconstriction to ET-1 (10(-10) M; P < 0.001 versus control). The thromboxane analogue (U-46619) reduced flow in a concentration-dependent manner (P < 0.001 versus control).
  
  
  CONCLUSIONS
  Endothelium-derived nitric oxide released under basal conditions or stimulated by bradykinin significantly regulated flow to the porcine ophthalmic microcirculation. This vasodilator system may play an important protective role against vasospasm. In contrast, ET-1 has vasodilator effects through the release of prostaglandins and potent vasoconstrictor properties mediated through ETA receptors.
authors.affiliation: Department of Research, University Hospital, Basel, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Meyer
authors.forename: J
authors.initials: J
authors.lastname: Flammer
authors.forename: T F
authors.initials: TF
authors.lastname: Lüscher
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001783:Blood Flow Velocity; D001920:Bradykinin / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005123:Eye / Q000098:blood supply*; D007211:Indoles / Q000494:pharmacology; D008833:Microcirculation; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D001381:Azepines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D014662:Vasoconstrictor Agents; C079574:FR 139317; D009569:Nitric Oxide; D001120:Arginine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester