In Vivo Evidence of an Endothelin-Induced Vasopressor Tone After Inhibition of Nitric Oxide Synthesis in Rats

• DOI: 10.1161/01.cir.91.3.771
• Publication Date: 2012-06-12T00:34:42Z
• Authors: Vincent Richard; Manuela Hogie; Martine Clozel; Bernd-Michael Lö...; Christian Thuillez
• Keywords: Endothelin receptor antagonist; Phenylephrine

Continuous production of nitric oxide (NO) from endothelial cells permanently inhibits the synthesis and vasoconstrictor effects endothelin. Thus, inhibition NO might unmask a vasopressor response to To assess whether endothelin contributes pressor induced by synthesis, we tested bosentan, nonpeptide antagonist ETA ETB receptors, affected hypertensive synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME).Anesthetized rats received increasing doses L-NAME (0.1 3 mg.kg-1) in absence or presence bosentan (3 mg.kg-1 IV 15 minutes before L-NAME). Bosentan itself did not affect blood pressure. dose-dependent increase mean arterial pressure (percent baseline after mg.kg-1, 25 +/- 5%), this was reduced (13 3%; P < .05) selective BQ-123 mg.kg-1: controls, 4%; BQ-123, 14 5%; .01). In contrast, phenylephrine (1 100 micrograms.kg-1). The also ganglion-blocked (chlorisondamine 2.5 89 10%; 45 7%) pithed (controls, 165 9%; 85 12%; inhibited another NG-nitro L-arginine normal 24 10 .01) 86 13%; 8%; rats. Finally, modest plasma levels endothelin-1 26.8 4.1 pg.mL-1; L-NAME, 38.5 3.3 .05).These experiments demonstrate that unmasks tonic influence endothelin, suggesting peptide could play major role pathophysiological situations associated with an impaired formation NO.