S. Greenacre et al., PEROXYNITRITE - A MEDIATOR OF INCREASED MICROVASCULAR PERMEABILITY, Clinical and experimental pharmacology and physiology, 24(11), 1997, pp. 880-882
1. Increased expression of inducible nitric oxide synthase (iNOS) and
subsequent elevation of nitric oxide (NO) levels at inflammatory sites
have led to the suggestion that peroxynitrite (the reaction product o
f superoxide and NO) is involved in proinflammatory processes. The pre
sent study has investigated the ability of peroxynitrite to induce oed
ema formation in the rat cutaneous microvasculature. 2. Peroxynitrite
was synthesized from hydrogen peroxide and acidified nitrite, Spectrop
hotometry was used to measure the concentration and breakdown of perox
ynitrite, It was also used to determine maximum amounts of hydrogen pe
roxide and sodium nitrite remaining after synthesis. 3. Oedema formati
on in response to intradermally (i.d.) injected peroxynitrite, hydroge
n peroxide and sodium nitrite was measured by the extravascular accumu
lation of i.v. [I-125]-albumin in the anaesthetized rat. 4. Peroxynitr
ite (40, 100 and 200 nmol/site) acted in a dose-dependent manner to ca
use a mean (+/- SEM) increase in plasma extravasation of 24 +/- 2, 55
+/- 5 and 69 +/- 6 mu L, respectively (n = 4), with resulting inflamma
tory oedema, Peroxynitrite induced significantly larger plasma extrava
sation than equivalent vehicle controls at doses of 100 (P > 0.05) and
200 mmol (P > 0.001). This increased extravasation appears to be a di
rect microvascular response to peroxynitrite administration and not du
e to either a raised pH, necessary to stabilize the peroxynitrite, or
contaminating concentrations of hydrogen peroxide or sodium nitrite fr
om which peroxynitrite is formed. 5. These results suggest that peroxy
nitrite acts to increase microvascular permeability and oedema formati
on, Therefore, peroxynitrite may mediate vascular pro-inflammatory eff
ects in addition to its direct cytotoxic activity.