Basic FGF enhances endothelium-dependent relaxation of the collateral-perfused coronary microcirculation.
The effect of chronic, periadventitial administration of basic (b) fibroblast growth factor (FGF) on endothelial dysfunction in the collateral-dependent and normally perfused coronary microcirculation was examined. Ameroid constrictors were placed on the proximal left circumflex coronary artery (LCX) in 23 pigs. In 11 pigs, bFGF was released from calcium alginate microcapsules into the perivascular space of the proximal left anterior descending coronary artery (LAD) and LCX. After 5-8 wk, coronary arterial microvessels (80-170 microns) were studied in a pressurized (40 mmHg) no-flow state with video microscopy. Receptor-mediated endothelium-dependent relaxations to ADP and serotonin were reduced while contraction to acetylcholine was enhanced in the collateral-dependent LCX microvessels of non-bFGF-treated control hearts. Relaxation of vessels to the non-receptor-mediated, endothelium-dependent agent A-23187; endothelium-independent relaxation to nitroprusside; and contraction to KCl were similar in all groups. Chronic treatment with bFGF normalized responses to ADP, serotonin, and acetylcholine in the collateral-dependent LCX region but had no effect on the responses of vessels in the normally perfused LAD region. Arteriolar density in the collateral-perfused LCX region of bFGF-treated hearts was markedly increased (4-fold compared with that in untreated hearts, suggesting a link between the angiogenic effect of bFGF and its action on endothelial preservation. Thus the periadventitial, sustained delivery of bFGF preserves receptor-mediated, endothelium-dependent responses in the collateral-dependent LCX region but has no effect on responses of microvessels in the normally perfused LAD region or on non-receptor-mediated endothelium-dependent relaxation.
Sellke
F W
FW
Department of Surgery, Beth Israel Hospital, Boston 02215.
Wang
S Y
SY
Friedman
M
M
Harada
K
K
Edelman
E R
ER
Grossman
W
W
Simons
M
M
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000464:Alginates; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004337:Drug Carriers; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D020723:Glucuronic Acid; D006321:Heart / Q000187:drug effects; D006603:Hexuronic Acids; D007213:Indomethacin / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009203:Myocardial Infarction / Q000139:chemically induced / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012685:Sepharose / Q000031:analogs & derivatives; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D000464:Alginates; D004337:Drug Carriers; D006603:Hexuronic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; C037405:heparin-sepharose; D016222:Fibroblast Growth Factor 2; D009599:Nitroprusside; D019335:Nitroarginine; D012701:Serotonin; D000001:Calcimycin; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D020723:Glucuronic Acid; D012685:Sepharose; D001120:Arginine; D007650:Ketanserin; D000109:Acetylcholine; D007213:Indomethacin