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Effect of the nitric oxide donor V-PYRRO/NO on portal pressure and sinusoidal dynamics in normal and cirrhotic mice.

Publication ,  Journal Article
Edwards, C; Feng, H-Q; Reynolds, C; Mao, L; Rockey, DC
Published in: Am J Physiol Gastrointest Liver Physiol
June 2008

Reduced sinusoidal endothelial nitric oxide (NO) production contributes to increased intrahepatic resistance and portal hypertension after liver injury. We hypothesized that V-PYRRO/NO, an NO donor prodrug metabolized "specifically" in the liver, would reduce portal venous pressure (PVP) without affecting the systemic vasculature. Liver injury was induced in male BALB/c mice by weekly CCl(4) gavage. PVP and mean arterial pressure were recorded during intravenous administration of V-PYRRO/NO. In vivo microscopy was used to monitor sinusoidal diameter and flow during drug administration. Mean PVP was increased in CCl(4)-treated mice compared with sham-treated mice. In dose-response experiments, the minimum dose of PYRRO/NO required to acutely lower PVP by 20%, the amount believed to yield a clinically meaningful outcome, was 200 nmol/kg. This dose decreased portal pressure in cirrhotic (23.4 +/- 2.0%, P < 0.001 vs. vehicle) and sham-treated (19.5 +/- 2.3%, P < 0.001 vs. vehicle) animals by a similar magnitude. This concentration also led to dilation of hepatic sinusoids and an increase in sinusoidal volumetric flow, consistent with a reduction of intrahepatic resistance. The effect of V-PYRRO/NO on mean arterial pressure was significant at all concentrations tested, including the lowest, 30 nmol/kg (P < 0.001 vs. vehicle for all doses). We conclude that V-PYRRO/NO had widespread vascular effects and, as such, is unlikely to be suitable for treatment of portal hypertension. As the potential of this or other similar compounds for treatment of portal hypertension is evaluated, effects on the systemic vasculature will also need to be considered.

Duke Scholars

Published In

Am J Physiol Gastrointest Liver Physiol

DOI

ISSN

0193-1857

Publication Date

June 2008

Volume

294

Issue

6

Start / End Page

G1311 / G1317

Location

United States

Related Subject Headings

  • Vasodilation
  • Reference Values
  • Pyrrolidines
  • Portal Pressure
  • Nitric Oxide Donors
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Liver Cirrhosis
  • Gastroenterology & Hepatology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Edwards, C., Feng, H.-Q., Reynolds, C., Mao, L., & Rockey, D. C. (2008). Effect of the nitric oxide donor V-PYRRO/NO on portal pressure and sinusoidal dynamics in normal and cirrhotic mice. Am J Physiol Gastrointest Liver Physiol, 294(6), G1311–G1317. https://doi.org/10.1152/ajpgi.00368.2007
Edwards, Claire, Hong-Qiang Feng, Christopher Reynolds, Lan Mao, and Don C. Rockey. “Effect of the nitric oxide donor V-PYRRO/NO on portal pressure and sinusoidal dynamics in normal and cirrhotic mice.Am J Physiol Gastrointest Liver Physiol 294, no. 6 (June 2008): G1311–17. https://doi.org/10.1152/ajpgi.00368.2007.
Edwards C, Feng H-Q, Reynolds C, Mao L, Rockey DC. Effect of the nitric oxide donor V-PYRRO/NO on portal pressure and sinusoidal dynamics in normal and cirrhotic mice. Am J Physiol Gastrointest Liver Physiol. 2008 Jun;294(6):G1311–7.
Edwards, Claire, et al. “Effect of the nitric oxide donor V-PYRRO/NO on portal pressure and sinusoidal dynamics in normal and cirrhotic mice.Am J Physiol Gastrointest Liver Physiol, vol. 294, no. 6, June 2008, pp. G1311–17. Pubmed, doi:10.1152/ajpgi.00368.2007.
Edwards C, Feng H-Q, Reynolds C, Mao L, Rockey DC. Effect of the nitric oxide donor V-PYRRO/NO on portal pressure and sinusoidal dynamics in normal and cirrhotic mice. Am J Physiol Gastrointest Liver Physiol. 2008 Jun;294(6):G1311–G1317.

Published In

Am J Physiol Gastrointest Liver Physiol

DOI

ISSN

0193-1857

Publication Date

June 2008

Volume

294

Issue

6

Start / End Page

G1311 / G1317

Location

United States

Related Subject Headings

  • Vasodilation
  • Reference Values
  • Pyrrolidines
  • Portal Pressure
  • Nitric Oxide Donors
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Liver Cirrhosis
  • Gastroenterology & Hepatology