Hemodynamic effects of intracoronary VEGF delivery: evidence of tachyphylaxis and NO dependence of response.
Vascular endothelial growth factor (VEGF) has been utilized to improve blood flow in the setting of myocardial or peripheral vascular ischemia. In this investigation we studied the hemodynamic effects of intracoronary VEGF administration. Hemodynamic parameters and Doppler flow wire recordings from the left anterior descending coronary artery were measured after intracoronary infusion of VEGF (1, 10, and 100 micrograms) in 28 intubated pigs. Additional studies were performed using an in vitro isolated microvessel preparation. VEGF produced a highly significant dose-dependent increase in coronary blood flow (maximal 3.51 +/- 0.85-fold) in the absence of significant changes in epicardial artery diameter, a decline in mean arterial pressure (maximal 43%), and a decrease in left ventricular end-diastolic pressure (maximal 52%), all of which could be inhibited by pretreatment with NG-nitro-L-arginine. The increase in coronary flow seen with 10 or 100 micrograms VEGF was significantly greater than the maximal vasodilation achieved with serotonin or nitroglycerin and was equivalent to a maximal adenosine response. In summary, VEGF stimulates nitric oxide (NO)-dependent dilation of coronary microvessels, and repeat administrations of VEGF resulted in rapid development of tachyphylaxis to VEGF as well as serotonin, but not to nitroglycerin or adenosine, which appeared to be secondary to impaired NO production.
Lopez
J J
JJ
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Laham
R J
RJ
Carrozza
J P
JP
Tofukuji
M
M
Sellke
F W
FW
Bunting
S
S
Simons
M
M
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D016228:Endothelial Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D007261:Infusions, Intra-Arterial; D008222:Lymphokines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D019335:Nitroarginine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D013618:Tachyphylaxis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014664:Vasodilation / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019335:Nitroarginine; D012701:Serotonin; D005996:Nitroglycerin; D000241:Adenosine