TY - JOUR
T1 - Intracavernosal injections of vascular endothelial growth factor protects endothelial dependent corpora cavernosal smooth muscle a relaxation in the hypercholesterolemic rabbit
T2 - A preliminary study
AU - Henry, G. D.
AU - Byrne, R.
AU - Hunyh, T. T.T.
AU - Abraham, V.
AU - Annex, B. H.
AU - Hagen, P. O.
AU - Donatucci, C. F.
N1 - Funding Information:
Animal care complied with the Guide for the Care and Use of Laboratory Animals issued by the National Institutes of Health (US Department of Health and Human Services) and the Principles of Laboratory Animal Care as formulated by the National Society for Medical Research. The Institutional Animal Care and Use Committee approved the experimental protocol.
PY - 2000
Y1 - 2000
N2 - Atherosclerosis is a major risk factor for erectile dysfunction, and loss of endothelium-dependent vasodilation appears early in the development of this disorder. Nitric oxide (NO) appears to be the principle mediator of erectile function and is generated in part by the sinusoidal endothelium. Vascular endothelial growth factor (VEGF) is an angiogenic growth factor and an endothelial cell-specific mitogen and the actions of VEGF are coupled to NO. In this preliminary study, we investigated whether VEGF could be used to protect endothelial dependent cavernosal relaxation from the atherosclerotic injury induced by a hypercholesterolemic diet. Two groups of New Zealand white adult male rabbits received a 1% cholesterol diet for four weeks, and two groups consumed normal rabbit chow. Half of the rabbits consuming the 1% cholesterol diet received weekly penile injections of 0.3 mg VEGF (n = 8), and half injections of normal saline (n = 8). Rabbits fed normal chow followed a similar protocol, half received weekly penile injections of 0.3 mg VEGF (n = 6) and half were given weekly penile injections of normal saline (n = 6). Isometric tension studies (with norepinephrine, acetylcholine, sodium nitroprusside and histamine) were performed on isolated strips of corpora cavernosa. The degree of corporal smooth muscle relaxation in response to ACH and SNP administration was recorded and compared. Significant elevation in serum total cholesterol levels occurred in rabbits receiving 4 weeks of the 1% cholesterol diet (727± 75.6 mg/dl vs 38.7± 5.53 mg/dl) P < 0.01. There were no significant differences in cavernosal contraction in any group, while cavernosal smooth muscle from rabbits on normal chow retained the ability to relax in response to ACH and SNP in tissue bath. The hypercholesterolemic rabbits receiving VEGF had a significantly higher maximal per-cent relaxation to ACH (111 ± 28.9) compared to the hypercholesterolemic rabbits that received NS (77 ± 23.1, P < 0.001). This difference in percent maximal relaxation to SNP was also present for hypercholesterolemic/VEGF rabbits (129.4± 24) versus the hypercholesterolemic/NS rabbits (115.0 ± 18, P=0.033). In conclusion, intracavernosal injections of VEGF appear to protect corporal endothelium from hypercholesterolemia induced injury, thus preserving endothelial dependent corporal smooth muscle relaxation in hypercholesterolemic rabbit.
AB - Atherosclerosis is a major risk factor for erectile dysfunction, and loss of endothelium-dependent vasodilation appears early in the development of this disorder. Nitric oxide (NO) appears to be the principle mediator of erectile function and is generated in part by the sinusoidal endothelium. Vascular endothelial growth factor (VEGF) is an angiogenic growth factor and an endothelial cell-specific mitogen and the actions of VEGF are coupled to NO. In this preliminary study, we investigated whether VEGF could be used to protect endothelial dependent cavernosal relaxation from the atherosclerotic injury induced by a hypercholesterolemic diet. Two groups of New Zealand white adult male rabbits received a 1% cholesterol diet for four weeks, and two groups consumed normal rabbit chow. Half of the rabbits consuming the 1% cholesterol diet received weekly penile injections of 0.3 mg VEGF (n = 8), and half injections of normal saline (n = 8). Rabbits fed normal chow followed a similar protocol, half received weekly penile injections of 0.3 mg VEGF (n = 6) and half were given weekly penile injections of normal saline (n = 6). Isometric tension studies (with norepinephrine, acetylcholine, sodium nitroprusside and histamine) were performed on isolated strips of corpora cavernosa. The degree of corporal smooth muscle relaxation in response to ACH and SNP administration was recorded and compared. Significant elevation in serum total cholesterol levels occurred in rabbits receiving 4 weeks of the 1% cholesterol diet (727± 75.6 mg/dl vs 38.7± 5.53 mg/dl) P < 0.01. There were no significant differences in cavernosal contraction in any group, while cavernosal smooth muscle from rabbits on normal chow retained the ability to relax in response to ACH and SNP in tissue bath. The hypercholesterolemic rabbits receiving VEGF had a significantly higher maximal per-cent relaxation to ACH (111 ± 28.9) compared to the hypercholesterolemic rabbits that received NS (77 ± 23.1, P < 0.001). This difference in percent maximal relaxation to SNP was also present for hypercholesterolemic/VEGF rabbits (129.4± 24) versus the hypercholesterolemic/NS rabbits (115.0 ± 18, P=0.033). In conclusion, intracavernosal injections of VEGF appear to protect corporal endothelium from hypercholesterolemia induced injury, thus preserving endothelial dependent corporal smooth muscle relaxation in hypercholesterolemic rabbit.
KW - Erectile dysfunction
KW - Hypercholesterolemia
KW - Impotence
KW - Nitric oxide
KW - Nitric oxide synthase
KW - Penis
KW - Rabbit
KW - Vascular endothelial growth factor
UR - http://www.scopus.com/inward/record.url?scp=0034472818&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034472818&partnerID=8YFLogxK
U2 - 10.1038/sj.ijir.3900621
DO - 10.1038/sj.ijir.3900621
M3 - Article
C2 - 11416837
AN - SCOPUS:0034472818
SN - 0955-9930
VL - 12
SP - 334
EP - 339
JO - International journal of impotence research
JF - International journal of impotence research
IS - 6
ER -