Peroxynitrite has potent pulmonary vasodilator activity in the rat Article

Full Text via DOI: 10.1139/Y2012-012 PMID: 22452357 Web of Science: 000302241200013

Cited authors

  • Casey, David B.; Pankey, Edward A.; Badejo, Adeleke M.; Bueno, Franklin R.; Bhartiya, Manish; Murthy, Subramanyam N.; Uppu, Rao M.; Nossaman, Bobby D.; Kadowitz, Philip J.


  • Peroxynitrite (PN) worsens pathological conditions associated with oxidative stress. However, beneficial effects have also been reported. PN has been shown to demonstrate vasodilator as well as vasoconstrictor properties that are dependent upon the experimental conditions and the vascular bed studied. PN-induced vascular smooth muscle relaxation may involve the formation of nitric oxide (NO) donors. The present results show that PN has significant vasodilator activity in the pulmonary and systemic vascular beds, and that responses to PN were not attenuated by L-penicillamine (L-PEN), a PN scavenger, whereas responses to sodium nitroprusside (SNP) were decreased. PN had a small inhibitory effect on decreases in arterial pressure in response to the NO donors diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA/NO) and S-nitrosoglutathione (GSNO). PN partially reversed hypoxic pulmonary vasoconstriction. PN responses were attenuated by the soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and responses to PN and the PN precursor, 3-morpholinosydnonimine (SIN-1), were different. These data show that PN has potent pulmonary vasodilator activity in the rat, and provide evidence that a PN interaction with S-nitrosothiols is not the major mechanism mediating the response. These data suggest that responses to PN are mediated by the activation of sGC, and that PN has a small inhibitory effect on NO responses.

Publication date

  • 2012

International Standard Serial Number (ISSN)

  • 0008-4212

Start page

  • 485

End page

  • 500


  • 90


  • 4