Inducible nitric oxide synthase modulates angiogenesis in ischemic hindlimb of rat.
BACKGROUND
Angiogenesis plays an important role in maintaining adequate oxygen delivery, and nitric oxide (NO) is a potential regulator of angiogenesis. NO is synthesized through three isoforms of NO synthase (NOS). It is hypothesized that the NO derived from inducible NOS (iNOS) may promote survival of ischemic tissue through angiogenesis. To test this hypothesis, we investigated the effect of iNOS deficiency (by L-NIL) on angiogenesis in a hindlimb ischemia model.


METHODS
Thirty-two male wistar rats randomly divided into four groups. In groups 1 & 2, hindlimb ischemia was induced by ligation of femoral artery and they received L-NIL and saline respectively. The animals in groups 3 and 4 also received L-NIL and saline respectively without surgical procedure. After 21 days, the serum concentration of nitrite, capillary density and expression of HIF1alpha were determined.


RESULTS
Serum nitrite levels were significantly lower in L-NIL groups (p<0.05). The capillary density in group 1 (ischemia+L-NIL) was significantly different from group 2 (ischemia+saline); group 1: 360.33+/-77.02, group 2: 549+/-81.85 /mm2, p<0.05) .In addition, expression of HIF1alpha was significantly increased in ischemic groups (p<0.05).


CONCLUSIONS
Selective inhibition of iNOS by L-NIL inhibits angiogenesis in a hindlimb ischemic rat model. In addition, ischemia induces expression of HIF1alpha in hypoxic tissue.
Nematollahi
Sedigheh
S
Department of Physiology, Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Nematbakhsh
Mehdi
M
Haghjooyjavanmard
Shaghayegh
S
Khazaei
Majid
M
Salehi
Mohammad
M
D000818:Animals; D002196:Capillaries / Q000033:anatomy & histology / Q000187:drug effects; D006614:Hindlimb; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II / Q000494:pharmacology*; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
D009573:Nitrites; D052247:Nitric Oxide Synthase Type II