Vascular Endothelial Growth Factor 121 Attenuates Hypertension, Myocardial Necrosis and Renal Injury‐induced by N ω ‐nitro‐L‐arginine Methyl Ester and Angiotensin II in Rats

Vascular Endothelial Growth Factor (VEGF) plays a critical role in maintaining integrity of endothelial cell by its diverse biological properties. We investigated the effects of VEGF121 on a rat cardiac‐injury model induced by N ω ‐nitro‐L‐arginine methyl ester, L‐NAME and Angiotensin II (Ang II). Male, Sprague‐Dawley rats were treated with L‐NAME (80mg/kg/day) and 1% NaCl in drinking water for 14 days followed by subcutaneous (s.c.) infusion of Ang II (0.35mg/kg/day) via an osmotic pump for 3 days from day 11. Control rats (n=6) received drinking water. VEGF121 (400μg/kg, n=10) or Vehicle (PBS, n=8) was given s.c. twice a day concurrently with Ang II for 3 days. Systolic blood pressure (SBP) was significantly increased in L‐NAME/Ang II‐treated rats compared to controls (172±17 vs 121±5mmHg, p<0.001). However, VEGF121 completely reversed SBP level to 108±16mmHg (p<0.001). The myocardial damage evaluated by the percentage of myocardial necrosis in both left and right ventricles was significantly reduced by VEGF121 (0.9±1.4 vs 5.8±3.7%, p<0.001). VEGF121 also attenuated the kidney damage measured by glomerular lesion index (18±24 vs 72±39, p<0.01). VEGF121 reduced the ratio of urinary albumin to creatinine levels (3083±4539 vs 55925±62315 μg/mg, p<0.05). These results suggest that VEGF121 is a cardio‐renal protective agent, and may have therapeutic applications in hypertension‐related diseases.