Pulmonary and systemic vasodilator responses to the soluble guanylyl cyclase stimulator, BAY 41-8543, are modulated by nitric oxide Article

Full Text via DOI: 10.1152/ajpheart.01101.2009 PMID: 20639220 Web of Science: 000283857300020

Cited authors

  • Badejo, Adeleke M., Jr.; Nossaman, Vaughn E.; Pankey, Edward A.; Bhartiya, Manish; Kannadka, Chandrika B.; Murthy, Subramanyam N.; Nossaman, Bobby D.; Kadowitz, Philip J.

Abstract

  • Badejo AM Jr, Nossaman VE, Pankey EA, Bhartiya M, Kannadka CB, Murthy SN, Nossaman BD, Kadowitz PJ. Pulmonary and systemic vasodilator responses to the soluble guanylyl cyclase stimulator, BAY 41-8543, are modulated by nitric oxide. Am J Physiol Heart Circ Physiol 299: H1153-H1159, 2010. First published July 16, 2010; doi:10.1152/ajpheart.01101.2009.-BAY 41-8543 is a nitric oxide (NO)-independent stimulator of soluble guanylyl cyclase (sGC). Responses to intravenous injections of BAY 41-8543 were investigated under baseline and elevated tone conditions and when NO synthase (NOS) was inhibited with N-omega-nitro-L-arginine methyl ester (L-NAME). Under baseline conditions, intravenous injections of BAY 41-8543 caused small decreases in pulmonary arterial pressure, larger decreases in systemic arterial pressure, and increases in cardiac output. When pulmonary arterial pressure was increased to similar to 30 mmHg with an intravenous infusion of U-46619, intravenous injections of BAY 41-8543 produced larger dose-dependent decreases in pulmonary arterial pressure, and the relative decreases in pulmonary and systemic arterial pressure in response to the sGC stimulator were similar. Treatment with L-NAME markedly decreased responses to BAY 41-8543 when pulmonary arterial pressure was increased to similar values (similar to 30 mmHg) in U-46619-infused and in U-46619-infused plus L-NAME-treated animals. The intravenous injection of a small dose of sodium nitroprusside (SNP) when combined with BAY 41-8543 enhanced pulmonary and systemic vasodilator responses to the sGC stimulator in L-NAME-treated animals. The present results indicate that BAY 41-8543 has similar vasodilator activity in the systemic and pulmonary vascular beds when pulmonary vasoconstrictor tone is increased with U-46619. These results demonstrate that pulmonary and systemic vasodilator responses to BAY 41-8543 are significantly attenuated when NOS is inhibited by L-NAME and show that vasodilator responses to BAY 41-8543 are enhanced when combined with a small dose of SNP in L-NAME-treated animals. The present results are consistent with the concept that pulmonary and systemic vasodilator responses to the sGC stimulator are NO-independent; however, the vasodilator activity of the compound is greatly diminished when endogenous NO production is inhibited with L-NAME. These data show that BAY 41-8543 has similar vasodilator activity in the pulmonary and systemic vascular beds in the rat.

Authors

Publication date

  • 2010

Published in

Category

International Standard Serial Number (ISSN)

  • 0363-6135

Start page

  • H1153

End page

  • H1159

Volume

  • 299

Issue

  • 4