Vascular endothelial growth factor restores corporeal smooth muscle function in vitro.
OBJECTIVE
The therapeutic use of vasculogenic growth factors has been successfully demonstrated in models of organ ischemia. We determined whether vascular endothelial growth factor (VEGF) would reverse corporeal smooth muscle dysfunction in the hypercholesterolemic rabbit model of erectile dysfunction.


METHODS
A total of 36 New Zealand White rabbits were fed a normal (12) or 1% cholesterol (24) diet and treated after 6 weeks with 0.9 mg. VEGF or vehicle. At 6 weeks 24 rabbits received a single intracavernous dose and 12 received a single intravenous bolus of either drug. Ten days after injection corporeal smooth muscle function was analyzed after relaxation to acetylcholine and sodium nitroprusside using isometric tension studies. Corporeal sections were assessed for smooth muscle content with f-actin staining and VEGF expression by immunohistochemical study and enzyme-linked immunosorbent assay.


RESULTS
Endothelium dependent (acetylcholine) and nitric oxide mediated (sodium nitroprusside) smooth muscle relaxation were impaired in cholesterol fed animals (p = 0.021 and 0.003, respectively). Intracavernous VEGF treatment restored sodium nitroprusside mediated relaxation to normal (p = 0.015) and intravenous VEGF restored acetylcholine and sodium nitroprusside mediated relaxation (p = 0.014 and 0.018, respectively). Decreased smooth muscle content was noted in cholesterol fed animals versus normal diet controls (p = 0.008), which was not affected by VEGF treatment (p = 0.450). Corporeal endothelial cell content was increased after intracavernous but not intravenous VEGF treatment (p = 0.001 and 0.385, respectively). VEGF expression was augmented after treatment with recombinant VEGF (p <0.001).


CONCLUSIONS
VEGF administration variably mitigated the impairment of corporeal smooth muscle relaxation in the hypercholesterolemic rabbit model of erectile dysfunction.
Division of Urology, Atherosclerosis Research Laboratory, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
R R
RR
Byrne
G D
GD
Henry
D S
DS
Rao
T T
TT
Huynh
A M
AM
Pippen
B H
BH
Annex
P O
PO
Hagen
C F
CF
Donatucci
D000818:Animals; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006937:Hypercholesterolemia / Q000503:physiopathology; D007150:Immunohistochemistry; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000187:drug effects / Q000503:physiopathology; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors