Neural and endothelial nitric oxide synthase activity in rat penile erectile tissue

Dail, William G.; Barba, Vera; Leyba, Leonard; Galindo, Rafael

doi:10.1007/s004410050463

Cited by 14 publications

(20 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…perimentally. Together, our present observations as well as the previous studies aforementioned (Schirar et al, 1994;Dail et al, 1995;Hedlund et al, 1999;Claudino et al, 2004;Teixeira et al, 2004a,b) rule out a significant role for endothelium-derived NO in the erectile responses of rat corpus cavernosum, thus explaining the poor acetylcholine-evoked relaxations as well as the lack of effect of L-NAME and ODQ to increase tone and to inhibit the relaxant responses induced by Rho-kinase inhibitors.…”

Section: ؉ Sensitization In Rat Corpus Cavernosumsupporting

confidence: 87%

“…positive NADPH diaphorase has been described in some parts of the sinusoidal endothelium of the rat penis (Keast, 1992), this has not been found in later investigations (Schirar et al, 1994;Dail et al, 1995;Hedlund et al, 1999). Bivalacqua et al (2004) have demonstrated that the RhoA/Rhokinase pathway down-regulates rat penile eNOS in diabetes and that inhibition of Rho-kinase led to a restoration of the erectile function, which was accompanied by an improvement of eNOS expression.…”

Section: ؉ Sensitization In Rat Corpus Cavernosummentioning

confidence: 94%

See 1 more Smart Citation

Proerectile Effects of the Rho-Kinase Inhibitor (S)-(+)-2-Methyl-1-[(4-methyl-5-isoquinolinyl)sulfonyl]homopiperazine (H-1152) in the Rat Penis

Teixeira¹,

Zhao²,

Webb³

2005

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

Section: ؉ Sensitization In Rat Corpus Cavernosumsupporting

confidence: 87%

Section: ؉ Sensitization In Rat Corpus Cavernosummentioning

confidence: 94%

Proerectile Effects of the Rho-Kinase Inhibitor (S)-(+)-2-Methyl-1-[(4-methyl-5-isoquinolinyl)sulfonyl]homopiperazine (H-1152) in the Rat Penis

Teixeira¹,

Zhao²,

Webb³

2005

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…Numerous NOS nerve fibers and a marked NOmediated neurogenic vasodilatation similar to that of penile arteries has also been reported for the human deep dorsal vein, 14,58 which probably allows the vessel to accommodate the expansion of the CCs during erection. In contrast, no nitrergic relaxation was found in human circumflex veins, 62 which is consistent with the scarcity of NOS fibers 58 and suggests that a passive compression by engorgement of cavernous spaces rather than active neurogenic mechanisms is responsible for variations of venous outflow in the smaller penile veins.…”

Section: Physiological Regulation Of Penile Vasodilatationmentioning

confidence: 67%

“…In contrast, no nitrergic relaxation was found in human circumflex veins, 62 which is consistent with the scarcity of NOS fibers 58 and suggests that a passive compression by engorgement of cavernous spaces rather than active neurogenic mechanisms is responsible for variations of venous outflow in the smaller penile veins. 14,62 The contribution of the different isoforms of NOS to penile erection has been a subject of debate, specially because erectile function and mating behavior are preserved in mice lacking the genes for eNOS and nNOS.…”

Section: Physiological Regulation Of Penile Vasodilatationmentioning

confidence: 69%

“…[55][56][57] nNOS has been found in the pelvic plexus and in terminal branches of the cavernous nerves innervating the trabecular smooth muscle and penile vasculature. 55,58 nNOS and vesicular ACh transporter (VAChT) are co-localized in most nerve terminals surrounding penile small arteries which suggests that ACh and NO coexist in the same parasympathetic cholinergic neurons that control penile arterial tone. 56,57 Earlier in vivo studies demonstrated that infusion of NOS inhibitors antagonized penile erection induced by pelvic stimulation and the nonadrenergic non-cholinergic (NANC) neurotransmitter mediating relaxation of the trabecular smooth muscle was later shown to be neural-released NO.…”

Section: Physiological Regulation Of Penile Vasodilatationmentioning

confidence: 99%

See 1 more Smart Citation

Physiological regulation of penile arteries and veins

2007

View full text Add to dashboard Cite

Recent experimental evidence suggests that arterial insufficiency precedes the structural and functional changes in corpora cavernosa (CC) leading to organic erectile dysfunction (ED). The present review gives an overview of the physiological factors involved in the regulation of penile vasculature. Sympathetic nerves maintain flaccidity and tonically released noradrenaline induces vasoconstriction of both arteries and veins through a 1 -and a 2 -postsynaptic receptors and downregulates its own release and that of nitric oxide (NO) through a 2 -presynaptic receptors. The sympathetic cotransmitter neuropeptide Y (NPY) modulates noradrenergic vasoconstriction in penile small arteries by both enhancing and depressing noradrenaline contractions through Y 1 -and Y 2 -postsynaptic and a NO-independent atypical endothelial receptor, respectively. Activation of a 1 -adrenoceptors involves both Ca 2 þ influx through L-type and receptor-operated Ca 2 þ channels (ROC) and Ca 2 þ sensitization mechanisms mediated by protein kinase C (PKC), tyrosine kinases (TKs) and Rho kinase (RhoK). In addition, RhoK can regulate Ca 2 þ entry in penile arteries upon receptor stimulation. Vasodilatation of penile arteries and large veins during erection is mediated by neurally released NO. The subsequent increased arterial inflow to the cavernosal sinoids and shear stress on the endothelium lining penile arteries activates endothelial NO production through Akt phosphorylation of endothelial NO synthase (eNOS). NO stimulates guanylate cyclase and increased cyclic guanin 3 0 -monophosphate (cGMP) levels in turn activate protein kinase G (PKG), which enhances K þ efflux through Ca 2 þ -activated (K Ca ) and voltage-dependent Ca 2 þ (K v ) channels in penile arteries and veins, respectively. PKG-mediated decrease in Ca 2 þ sensitivity and its regulation by RhoK remains to be clarified in penile vasculature. Phosphodiesterase type 5 (PDE5) inhibitors are potent vasodilators of penile resistance arteries and increase the content and effects of basally released endothelial NO. Endothelium-dependent relaxations of penile small arteries also include an endothelium-derived hyperpolarizing factor (EDHF)-type response, which is impaired in diabetes and hypertension-associated ED. Locally produced contractile and relaxant prostanoids regulate penile venous and arterial tone, respectively. The latter activates prostaglandin I (IP) and prostaglandin E (EP) receptors coupled to adenylate cyclase and to the increase of cyclic adenosine monophosphate (cAMP) levels, which in turn stimulates K þ efflux through ATPsensitive K þ (K ATP ) channels. There is a crosstalk between the cGMP and cAMP signaling pathways in penile small arteries. Relevant issues such as the mechanisms underlying the excitationsecretion coupling of the endothelial cells, as well as those involved in cell proliferation and vascular remodeling of the penile vasculature remain to be elucidated. In addition, only few studies have investigated the changes in structure and function of penile a...

show abstract

Nitric Oxide Induces Oxidative Stress and Mediates Cytotoxicity to Human Cavernosal Cells in Culture

RAJASEKARAN,

HELLSTROM,

SIKKA

2001

Journal of Andrology

View full text Add to dashboard Cite

Nitric oxide (NO) is a product of nitric oxide synthase (NOS) activity and is recognized as the main mediator of penile erection by induction of cavernosal smooth muscle relaxation. Although excessive NO can be generated via inducible NOS activation under certain inflammatory and noninflammatory conditions, for example, in response to TGF‐β and γ‐IFN (the proinflammatory cytokines), the effect of excessive NO produced as reactive nitrogen radical (NO) in the corpora cavernosa is not known. The present study was designed to evaluate whether the effect of NO on human cavernosal cells in primary culture is via oxidative stress. Cell growth was monitored by DNA synthesis, and mitochondrial function was evaluated by adenosine triphosphate (ATP) production. Primary culture was initiated with explants from human corpora cavernosa, and the monolayer cavernosal cells (passage 2–3) were plated on 12‐well tissue culture plates. At 70%‐80% confluency, the cells were incubated with varying concentrations of sodium nitroprusside(SNP) for 16 hours. The cell growth (DNA synthesis) was monitored by measuring [3H] thymidine incorporation, ATP levels (nanomoles per 104 cells) were measured by chemiluminescence assay using a lu‐minometer, the total oxidative stress was monitored by measuring the levels of 8‐iso PGF2α (picograms per milliliter) by using an enzyme‐linked immunosorbent assay kit, and NO production was monitored by accumulation of nitrite levels (micrometer per 104 cells). Human cavernosal smooth muscle cells (HCSMC) exposed to SNP (0 to 0.8 mM) exhibited a dose‐dependent (two‐ to fivefold) decrease in DNA and ATP synthesis, accompanied by a two‐ to threefold increase in the levels of 8‐iso PGF2α and about an eightfold increase in nitrite accumulation. These findings suggest that the NO released by SNP (>0.8 mM) exhibited a significant cytotoxicity to HCSMC, mediated by increased oxidative stress to these cells.

show abstract

Neural and endothelial nitric oxide synthase activity in rat penile erectile tissue

Cited by 14 publications

References 0 publications

Proerectile Effects of the Rho-Kinase Inhibitor (S)-(+)-2-Methyl-1-[(4-methyl-5-isoquinolinyl)sulfonyl]homopiperazine (H-1152) in the Rat Penis

Proerectile Effects of the Rho-Kinase Inhibitor (S)-(+)-2-Methyl-1-[(4-methyl-5-isoquinolinyl)sulfonyl]homopiperazine (H-1152) in the Rat Penis

Physiological regulation of penile arteries and veins

Nitric Oxide Induces Oxidative Stress and Mediates Cytotoxicity to Human Cavernosal Cells in Culture

Contact Info

Product

Resources

About