Previous studies demonstrated that cultured smooth muscle cells from corpus cavernosum display significantly altered K+ channel function, PGE-induced cAMP accumulation, and endothelin-1 induced Ca2+ mobilization that are consistent with the pathophysiology of erectile dysfunction.
The data obtained indicate that neither the expression levels nor the sequence deviations of PDE3A are the main reasons for erectile dysfunction in men.
We investigated the relationship between gene polymorphism in the angiotensin converting enzyme (ACE) or endothelial nitric oxide synthase (ecNOS) and development of erectile dysfunction.
Here we describe positional cloning of the gene responsible for an autosomal recessive CL/P-ectodermal dysplasia (ED) syndrome (CLPED1; previously ED4; ref.
Determination of human angiotensin converting enzyme (ACE) gene polymorphisms in erectile dysfunction: frequency differences of ACE gene polymorphisms according to the method of analysis.
When compared to normal human cavernosal tissue, diabetic corpus cavernosum from humans with erectile dysfunction had higher levels of arginase II protein, gene expression, and enzyme activity.
In 113 men with erectile dysfunction and 111 healthy male controls genotype status of the GNB3C825T polymorphism was determined by polymerase chain reaction and restriction analysis.
Given that human arginase II appears to play a role in regulating l-arginine bioavailability to NO synthase in human penile corpus cavernosum smooth muscle, the inhibition of human arginase II is a potential new strategy for the treatment of erectile dysfunction [Kim, N. N., Cox, J. D., Baggio, R. F., Emig, F. A., Mistry, S., Harper, S. L., Speicher, D. W., Morris, S. M., Ash, D. E., Traish, A. M., and Christianson, D. W. (2001) Biochemistry 40, 2678-2688].
In conclusion, our data showed no correlations of a novel polymorphism of the PDE5A promoter gene with the intermediate phenotype EH/ED and the BP and HR response to sildenafil administration.
Gene therapy to the penile corpora cavernosa of cDNAs expressing PnNOS or eNOS, or counteracting PIN, has been effective in ameliorating ED in the aging rat model that exhibits both neurogenic ED and CVOD. cDNA constructs for other genes involved in the control of penile erection have also been successfully tested.
Based on animal and cell studies, neurogenic ED is assumed to be caused mainly by: (a) an insufficient synthesis of nitric oxide (NO) due to a decrease in the levels of the penile neuronal nitric oxide synthase (PnNOS) or the impairment of its regulation by protein effectors (NMDA receptor, protein inhibitor of nNOS: PIN), occurring in the neuronal bodies or nerve terminals, or (b) a loss of the cells themselves by apoptosis caused by the induction of inducible NOS (iNOS) and the production of peroxynitrite.
Based on animal and cell studies, neurogenic ED is assumed to be caused mainly by: (a) an insufficient synthesis of nitric oxide (NO) due to a decrease in the levels of the penile neuronal nitric oxide synthase (PnNOS) or the impairment of its regulation by protein effectors (NMDA receptor, protein inhibitor of nNOS: PIN), occurring in the neuronal bodies or nerve terminals, or (b) a loss of the cells themselves by apoptosis caused by the induction of inducible NOS (iNOS) and the production of peroxynitrite.
Gene therapy to the penile corpora cavernosa of cDNAs expressing PnNOS or eNOS, or counteracting PIN, has been effective in ameliorating ED in the aging rat model that exhibits both neurogenic ED and CVOD. cDNA constructs for other genes involved in the control of penile erection have also been successfully tested.
Moreover, S100A8/A9 transferred the cofactor arachidonic acid to NADPH oxidase as shown by the impotence of a mutant S100A8/A9 complex unable to bind arachidonic acid to enhance NADPH oxidase activity.
Moreover, S100A8/A9 transferred the cofactor arachidonic acid to NADPH oxidase as shown by the impotence of a mutant S100A8/A9 complex unable to bind arachidonic acid to enhance NADPH oxidase activity.
In this paper, we report the case of a young man with homozygote genotype mutated with 5-methylenetetrahydrofolate reductase (MTHFR) thermolabile variant who, in the absence of relational stress, developed an erectile dysfunction (ED) refractory to the vasoactive type-V phosphodiesterase (PDE5) inhibitor therapy.
Only about 50% to 60% of these cases benefit from PDE5 inhibitor therapy, prompting the development of new approaches, including gene-based therapies for the treatment of ED.
In conclusion, the present study suggests that the LPC, a major component of oxidized low-density lipoprotiens, increases calcium in corporal smooth muscle cells probably through activation of a TRPC6 channel and the increased [Ca2+]i by LPC via TRP channels is one of mechanisms for hypercholesterolemia-induced erectile dysfunction.
In conclusion, the present study suggests that the LPC, a major component of oxidized low-density lipoprotiens, increases calcium in corporal smooth muscle cells probably through activation of a TRPC6 channel and the increased [Ca2+]i by LPC via TRP channels is one of mechanisms for hypercholesterolemia-induced erectile dysfunction.