Molecular and pharmacological approaches to inhibiting nitric oxide after burn trauma

Jean White, Deborah L. Carlson, Marita Thompson, David L. Maass, Billy Sanders, Brett Giroir, Jureta W. Horton

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Whereas controversial, several studies have suggested that nitric oxide (NO) alters cardiac contractility via cGMP, peroxynitrite, or poly(ADP ribose) synthetase (PARS) activation. This study determined whether burn-related upregulation of myocardial inducible NO synthase (iNOS) and NO generation contributes to burn-mediated cardiac contractile dysfunction. Mice homozygous null for the iNOS gene (iNOS knockouts) were obtained from Jackson Laboratory. iNOS knockouts (KO) as well as wild-type mice were given a cutaneous burn over 40% of the total body surface area by the application of brass probes (1 × 2 × 0.3 cm) heated to 100°C to the animals' sides and back for 5 s (iNOS/KO burn and wild-type burn). Additional groups of iNOS KO and wild-type mice served as appropriate sham burn groups (iNOS/KO sham and wild-type sham). Cardiac function was assessed 24 h postburn by perfusing hearts (n = 7-10 mice/group). Burn trauma in wild-type mice impaired cardiac function as indicated by the lower left ventricular pressure (LVP, 67 ± 2 mmHg) compared with that measured in wild-type shams (94 ± 2 mmHg, P < 0.001), a lower rate of LVP rise (+dP/dtmax, 1,620 ± 94 vs. 2, 240 ± 58 mmHg/s, P < 0.001), and a lower rate of LVP fall (-dP/dtmax, 1,200 ± 84 vs. 1,800 ± 42 mmHg/s, P < 0.001). Ventricular function curves confirmed significant contractile dysfunction after burn trauma in wild-type mice. Burn trauma in iNOS KO mice produced fewer cardiac derangements compared with those observed in wild-type burns (LVP: 78 ± 5 mmHg; +dP/dt: 1,889 ± 160 mmHg/s; -dP/dt: 1, 480 ± 154 mmHg/s). The use of a pharmacological approach to inhibit iNOS (aminoguanidine, given ip) in additional wild-type shams and burns confirmed the iNOS KO data. Whereas the absence of iNOS attenuated burn-mediated cardiac contractile dysfunction, these experiments did not determine the contribution of cardiac-derived NO versus NO generated by immune cells. However, our data indicate a role for NO in cardiac dysfunction after major trauma.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number4 54-4
StatePublished - Oct 1 2003

Fingerprint

Nitric Oxide Synthase
Nitric Oxide
Pharmacology
Wounds and Injuries
Burns
Knockout Mice
Poly Adenosine Diphosphate Ribose
Peroxynitrous Acid
Ventricular Function
Body Surface Area
Nitric Oxide Synthase Type II
Ventricular Pressure
Ligases
Up-Regulation
Skin

Keywords

  • Cardiomyocyte secretion of nitric oxide
  • Inducible nitric oxide
  • Langendorff perfused hearts
  • Left ventricular function
  • Mouse model of burn trauma

ASJC Scopus subject areas

  • Physiology

Cite this

Molecular and pharmacological approaches to inhibiting nitric oxide after burn trauma. / White, Jean; Carlson, Deborah L.; Thompson, Marita; Maass, David L.; Sanders, Billy; Giroir, Brett; Horton, Jureta W.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 285, No. 4 54-4, 01.10.2003.

Research output: Contribution to journalArticle

White, Jean ; Carlson, Deborah L. ; Thompson, Marita ; Maass, David L. ; Sanders, Billy ; Giroir, Brett ; Horton, Jureta W. / Molecular and pharmacological approaches to inhibiting nitric oxide after burn trauma. In: American Journal of Physiology - Heart and Circulatory Physiology. 2003 ; Vol. 285, No. 4 54-4.
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