Intracavernosal basic fibroblast growth factor improves vasoreactivity in the hypercholesterolemic rabbit.
OBJECTIVE
We determined the effects of intracavernosal injection (ICI) of recombinant basic fibroblast growth factor (rbFGF) on corporal tissue in hypercholesterolemic rabbits.


METHODS
Twenty New Zealand White rabbits were fed a 1% cholesterol diet for 6 weeks and were randomly divided into four groups. Group 1 (N = 5) received an ICI of phosphate buffered saline solution (PBS) once and again 3 weeks later. Group 2 (N = 4) received an ICI of 2.5 microg rbFGF once and PBS 3 weeks later. Group 3 (N = 6) received an ICI of 2.5 microg rbFGF once and again 3 weeks later. Group 4 (N = 5) received an ICI of 2.5 microg rbFGF once. All animals were maintained on the high cholesterol diet until sacrifice, 3 weeks after last injection. Strips of corporal tissue were submaximally contracted with norepinephrine, and dose-response curves were generated to evaluate endothelial-dependent (acetylcholine, ACH) and endothelial-independent (sodium nitroprusside, SNP) vasoreactivity. Protein levels of bFGF and vascular endothelial growth factor (VEGF) were assessed by enzyme-linked immunosorbent assay. Neuronal nitric oxide synthase (nNOS) protein and mRNA were detected by Western blot and semi-quantitative polymerase chain reaction, respectively.


RESULTS
Vasoreactivity was improved by bFGF treatment as shown by higher ED50[-log(M)] of ACH and SNP in Groups 2, 3, and 4. The expression of bFGF protein, VEGF protein, nNOS protein, and mRNA were all increased after bFGF treatment.


CONCLUSIONS
ICI of bFGF improved vasoreactivity in hypercholesterolemic rabbit corporal tissue, offering a new direction to explore for the treatment of erectile dysfunction.
Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC, USA.
Donghua
D
Xie
Anne M
AM
Pippen
Shelley I
SI
Odronic
Brian H
BH
Annex
Craig F
CF
Donatucci
D000818:Animals; D015153:Blotting, Western; D002784:Cholesterol / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000503:physiopathology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000098:blood supply / Q000187:drug effects; D010413:Penis / Q000098:blood supply* / Q000187:drug effects; D011817:Rabbits; D011897:Random Allocation; D012965:Sodium Chloride / Q000008:administration & dosage; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D012965:Sodium Chloride; D002784:Cholesterol