Hemodynamic effects of scatter factor in conscious rats.
Scatter factor (SF), also known as hepatocyte growth factor, is a potent mitogen that has been suggested to exhibit greater efficacy than vascular endothelial growth factor (VEGF) in rabbits with hindlimb ischemia. Our study examined the effects of SF on cardiovascular hemodynamics and compared the responses to VEGF. Hemodynamic parameters were monitored before and after administration of SF or VEGF in conscious, instrumented rats. Intravenous injection of SF produced a dose-related reduction in mean arterial pressure (MAP) and increase in heart rate (HR). These responses were significantly attenuated by pretreatment with N omega-nitro-L-arginine methyl ester a nitric oxide (NO) synthase inhibitor, suggesting the depressor effect of SF may be mediated by NO. SF (250 micrograms/kg) reduced stroke volume and cardiac output, but did not affect the maximal first derivation of left ventricular pressure (dP/dt), suggesting that the reduction in cardiac output is caused by decreased stroke volume that probably results from a reduction in venous return. Compared with SF, VEGF produced greater hypotensive and tachycardic responses and greater reductions in stroke volume and cardiac output, indicating that SF has fewer side effects on hemodynamics. Although both growth factors might reduce venous return, SF decreased hematocrit presumably through venodilation, whereas VEGF increased hematocrit as a result of vascular hyperpermeability.
Yang
R
R
Department of Cardiovascular Research, Genentech, Inc., South San Francisco, California 94080, USA.
Bunting
S
S
Ko
A
A
Schwall
R
R
Jin
H
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects*; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016276:Ventricular Function / Q000187:drug effects
D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D017228:Hepatocyte Growth Factor; D019331:NG-Nitroarginine Methyl Ester