BACKGROUND: We evaluated the effect of hypertension on hemodynamic responses and serum nitrite concentrations in normotensive (NT) and deoxycorticosteron acetate (DOCA)-Salt hypertensive (HT) rats. METHODS: Uncontrolled hemorrhagic shock was induced in NT and HT rats (n=7 each) by preliminary bleed of 25 ml/kg followed by a 75% tail amputation. The mean arterial pressure (MAP), heart rate and serum nitrite were measured pre-hemorrhage and during hemorrhage. RESULTS: Changes in time-averaged MAP after hemorrhage were significantly greater in HT group than NT. After resuscitation, the HT rats failed to restore MAP to baseline level. Serum nitrite level in both groups was significantly increased during shock period. Survival rate of HT animals was lower than NT group, although it was not statistically significant. CONCLUSIONS: Marked reduction of MAP and less improvement after resuscitation suggested the less adaptation of cardiovascular system in HT animals which may interfere with management of these subjects during uncontrolled hemorrhagic shock.
- MeSH
- arteriální tlak * MeSH
- chlorid sodný farmakologie MeSH
- dusitany krev MeSH
- hemoragický šok krev komplikace patofyziologie MeSH
- hypertenze komplikace MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- resuscitace MeSH
- srdeční frekvence * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: There is increasing evidence that peroxisome proliferator-activated receptors (PPARs) may be involved in the regulation of angiogenesis. In this study, we examined whether rosiglitazone, a PPARγ agonist, can restore angiogenesis in a rat hindlimb ischemia model of diabetes. METHODS: Male wistar rats were divided into four groups (n=6 each): control, diabetic and control and diabetic rats who received rosiglitazone (8 mg/kg/day). Diabetes was induced by streptozotocin (55 mg/kg; ip). After 21 days, serum concentrations of nitric oxide (NO), vascular endothelial growth factor (VEGF) and soluble VEGF receptor-2 (VEGFR-2) were measured and neovascularization in ischemic legs was evaluated by immunohistochemistry. RESULTS: Capillary density and capillary/fiber ratio in hindlimb ischemia of diabetic animals were significantly lower than the control group (P<0.05). Rosiglitazone significantly restored neovascularization in diabetic animals (P<0.05). CONCLUSIONS: rosiglitazone enhances neovascularization in diabetic ischemic skeletal muscle and could be considered for treatment of peripheral artery disease in diabetic subjects.
- MeSH
- biologické modely MeSH
- experimentální diabetes mellitus patofyziologie MeSH
- fyziologická neovaskularizace účinky léků MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- thiazolidindiony farmakologie MeSH
- zadní končetina krevní zásobení MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Background. Angiotensin-converting enzyme inhibitors have different effects on the cardiovascular system. The aim of this study was to investigate the effect of enalapril on skeletal muscle angiogenesis in diabetic and diabetic hind limb ischemic rats. Methods. We studied 24 male diabetic rats (induced by streptozotocin, 55 mg/kg, ip) divided into four groups. Groups 1 and 2 were diabetic sham (surgical procedure without femoral artery ligation). Groups 3 and 4 were diabetic animals subjected to induced hind limb ischemia. Groups 2 and 4 received enalapril (15 mg/kg/day, i.p) and groups 1 and 3 received an equal volume of saline. After 21 days, capillary density, capillary to fiber (cap/fib) ratio and serum concentrations of nitric oxide (NO), Vascular Endothelial Growth Factor (VEGF) and soluble VEGF Receptor-1 (sVEGF-R1) were evaluated. Results. Enalapril significantly increased serum NO and VEGF concentrations and reduced serum sVEGF-R1 concentrations in diabetic sham and hind limb ischemic rats (p<0.05). Administration of enalapril significantly increased capillary density and cap/fib ratio in diabetic sham and hind limb ischemic animals compared with nontreated groups (p<0.05). Conclusions. Enalapril restores skeletal muscle angiogenesis in diabetic hind limb ischemia and can be considered for the prevention and treatment of peripheral artery disease in diabetic subjects.
- MeSH
- diabetické angiopatie farmakoterapie patofyziologie MeSH
- enalapril farmakologie MeSH
- experimentální diabetes mellitus patofyziologie MeSH
- fyziologická neovaskularizace účinky léků MeSH
- inhibitory ACE farmakologie MeSH
- ischemie farmakoterapie patofyziologie MeSH
- kosterní svaly krevní zásobení MeSH
- krysa rodu rattus MeSH
- oxid dusnatý krev MeSH
- potkani Wistar MeSH
- receptory vaskulárního endoteliálního růstového faktoru krev MeSH
- vaskulární endoteliální růstový faktor A krev MeSH
- zadní končetina krevní zásobení MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
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). CONCLUSION: 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.
- MeSH
- dusitany krev MeSH
- fyziologická neovaskularizace účinky léků MeSH
- ischemie patofyziologie MeSH
- kapiláry anatomie a histologie účinky léků MeSH
- kosterní svaly krevní zásobení MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- synthasa oxidu dusnatého, typ II farmakologie MeSH
- zadní končetina MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH