Prevention of Renal Damage by Angiotensin II Blockade, Accompanied by Increased Renal Hepatocyte Growth Factor in Experimental Hypertensive Rats

Hepatocyte growth factor (HGF) is a unique growth factor that has many protective functions against renal damage. Our previous study demonstrated that HGF stimulated the growth of endothelial and epithelial cells without the replication of mesangial cells. Moreover, angiotensin (Ang) II significantly decreased local HGF production in mesangial cells. Therefore, we examined the effects of Ang II blockade on renal HGF expression and renal damage in experimental hypertensive rats. An angiotensin-converting enzyme inhibitor (cilazapril; 10 mg [middle dot] kg [middle dot] d), an Ang II type 1 receptor antagonist (E-4177; 30 mg [middle dot] kg [middle dot] d), hydralazine (8 mg [middle dot] kg [middle dot] d), and vehicle were administered to 16-week-old stroke-prone spontaneously hypertensive rats (SHR-SP) for 3 weeks. Renal damage was evaluated with a computer analysis system, and renal HGF mRNA was measured by Northern blot analysis. Blood pressure of SHR-SP was significantly decreased by all drug treatments compared with vehicle. Moreover, cilazapril, E-4177, and hydralazine significantly decreased the thickening and necrosis of blood vessels compared with vehicle. Similarly, degeneration and necrosis of glomeruli were also markedly improved by cilazapril and E-4177 (P