Nitrergic neurotransmission mediates the non‐adrenergic non‐cholinergic responses in the clitoral corpus cavernosum of the rabbit

Cellek, Selim; Moncada, Salvador

doi:10.1038/sj.bjp.0702278

Cited by 73 publications

(72 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…9 The vasoconstrictor neurotransmitter NA is also known to increase in concentration in a variety of tissues including the rat heart, tail artery and whole penis, [10][11][12] and the time course of these changes often involves a peak in concentration that can occur after several, or many months of hyperglycaemia. However, while some authors have found a reduction in the noradrenergic [13][14][15] and nitrergic 16,17 innervation in diabetic erectile tissue, the results on the noradrenergic nerves are not confirmed in a recent publication 12 and in the present work. Changes in the concentration of NA in the CC may or may not influence erectile function, depending on when and where there is an increased release, and indeed if there is a change in release at all, one might expect the inhibition of erection 18,19 and facilitation of detumescence.…”

Section: Introductioncontrasting

confidence: 55%

“…Other authors who have suggested that the autonomic nitrergic nerves to the CC of the rabbit clitoris degenerate in diabetics, have also used treatment regimes that induce a severe form of the diabetes. 16,17 It should also be recognized that there are considerable differences in the innervation of urogenital tissues in the two sexes, which is backed up by a considerable literature indicating the differential sensitivity of the neurones involved to androgens and estrogens. [27][28][29] The present study extends these observations and shows that great changes occur within the erectile tissue of the CC, smaller but significant changes in the GP, but no change in the adjacent urethra.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat

et al. 2007

View full text Add to dashboard Cite

The noradrenaline (NA) concentration in the rat corpus cavernosum (CC) increased to approximately 350% of control values after about 8 weeks of hyperglycaemia induced by the intraperitoneal injection of streptozotocin (STZ) at 10 weeks of age. These changes were maintained for at least a further 32 weeks of hyperglycaemia and occurred without any significant change in the weight in the tissue. Smaller but significant increases in NA concentration occurred in the glans penis (GP) reaching 150-175% of the control levels during the period of prolonged hyperglycaemia. In contrast, there was no significant change in the NA concentration in the penile urethra. Measurements have also been made that relate to changes in the synthesis and reuptake of NA in the CC during the period during which high NA concentration is maintained. Immunohistochemical studies for the synthetic enzyme tyrosine hydroxylase in the CC indicate that the intensity of staining in the tissue had increased after 10, 20 and 32 weeks of hyperglycaemia, relative to the tissues from control animals. Dilated nerve fibres and engorged endings were present in the CC of the diabetic animals at these times. Reuptake of tritiated NA by the terminal axonal membranes in the CC was raised to 181% of control values after 12 weeks of hyperglycaemia (Po0.05), but later declined to values that are not significantly different from the control levels (after 26 and 64 weeks of hyperglycaemia). There are few studies of the effects of prolonged diabetes on functional aspects of sympathetic postganglionic neurones in the CC, and this paper suggests that the changes described represent remodelling of noradrenergic axonal terminals starting about after 8-10 weeks of hyperglycaemia; this delay in onset of the neuropathic changes is also a feature of type I diabetes in humans.

show abstract

Section: Introductioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Recent studies have begun to unravel peripheral biochemical mediators involved in regulating genital engorgement/swelling and lubrication. The increased genital vasocongestion is thought to occur via activation of the parasympathetic nerves releasing physiological mediators such as nitric oxide; 8 it has been demonstrated that inhibition of nitric oxide synthesis with L-NAME (nitro-L-arginine-methyl ester), a nitric oxide synthase inhibitor, markedly attenuated genital blood flow and administration of sildenafilenhanced genital blood flow in response to pelvic nerve stimulation. 9 Moreover, CRP, at concentrations known to predict diverse vascular insults, profoundly quenches nitric oxide synthesis, while augmenting the release of endothelin-1 and upregulating adhesion molecules and chemoattractant chemokines, uncovering a proinflammatory and proatherosclerotic phenotype.…”

Section: Discussionmentioning

confidence: 99%

The metabolic syndrome: a cause of sexual dysfunction in women

et al. 2005

View full text Add to dashboard Cite

Female sexual dysfunction (FSD) is a significant public health problem. We assessed the prevalence of FSD in premenopausal women with the metabolic syndrome as compared to the general female population. Compared with the control group (N ¼ 80), women with the metabolic syndrome (N ¼ 120) had reduced mean full Female Sexual Function Index (FSFI) score (23.275.4 vs 30.174.7, Po0.001), reduced satisfaction rate (3.571.1 vs 4.771.2, Po0.01), and higher circulating levels of C-reactive protein (CRP: 2.2 (0.6/4.9) vs 0.8 (0.2/2.9) mg/l, median (interquartile range), P ¼ 0.01). There was an inverse relation between CRP levels and FSFI score (r ¼ À0.32, P ¼ 0.02). Investigation of female sexuality is suggested for patients with the metabolic syndrome.

show abstract

“…[2][3][4] Although the neurogenic control of the vascular events in these tissues has not been thoroughly investigated, it is known that the nitric oxide (NO)/cGMP pathway mediates the neurogenic relaxation of rabbit clitoral corpus cavernosum and is involved in the neurogenic relaxation of rabbit vagina. [5][6][7] Vardenafil is a potent and selective type 5 phosphodiesterase (PDE5) inhibitor that enhances NO-mediated relaxation of human corpus cavernosum and NO-induced rabbit penile erection, and it has been reported to potentiate erectile function in patients. 8,9 Furthermore, vardenafil is currently under clinical investigation for the treatment of erectile dysfunction (ED).…”

Section: Introductionmentioning

confidence: 99%

Vardenafil enhances clitoral and vaginal blood flow responses to pelvic nerve stimulation in female dogs

Angulo

Cuevas

et al. 2003

Int J Impot Res

View full text Add to dashboard Cite

The relaxation of the smooth muscle in the vagina and clitoris and the increase of blood flow into these organs is thought to be essential in the female sexual response. Vardenafil is a type 5 phosphodiesterase (PDE5) inhibitor that potentiates the nitric oxide (NO)/cGMP pathway facilitating penile smooth muscle relaxation and improving penile erection in men. Although the potentiation of the NO/cGMP pathway through PDE5 inhibitors can clearly enhance blood flow into the penis and is used in the therapy of male sexual dysfunction, there is controversy about the efficacy of these agents in improving female sexual function. The aim of this work was to evaluate the effects of vardenafil on the increase of blood flow into the vagina and clitoris induced by pelvic nerve electrical stimulation (PNES) in a female dog model. Application of PNES produced consistent and frequency-related increased blood flow into the vagina and clitoris of anesthetized female dogs. The magnitude and duration of the blood flow responses to PNES were variable among the different animals but remained stable over time within the same animal. The intravenous administration of vardenafil (1 mg/kg) significantly potentiated the increases in blood flow produced by PNES into the vagina (381.4 and 206.2% of control response at 5 and 10 Hz, respectively, Po0.01, n ¼ 6) and clitoris (379.4 and 238.5% of control response at 5 and 10 Hz, respectively, Po0.01, n ¼ 6) 20 min after administration. The significant enhancement of PNESinduced responses was maintained 50 min (224.5 and 181.0%, Po0.01 in vagina; 294.8 and 258.9%, Po0.05 in clitoris) and 80 min after vardenafil administration (209.5 and 156.9%, Po0.05 in vagina; 268.9 and 194.9%, Po0.05 in clitoris). Here we present a feasible model for research into female sexual function. Our results show that vardenafil effectively potentiates the blood flow responses to PNES in the genitalia of female dogs. These results emphasize the role of the NO/cGMP pathway in the local vasodilatory response in female sexual organs and provide a rationale for testing PDE5 inhibitors, such as vardenafil, as a treatment for certain forms of female sexual dysfunction.

show abstract

Nitrergic neurotransmission mediates the non‐adrenergic non‐cholinergic responses in the clitoral corpus cavernosum of the rabbit

Cited by 73 publications

References 9 publications

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat

The metabolic syndrome: a cause of sexual dysfunction in women

Vardenafil enhances clitoral and vaginal blood flow responses to pelvic nerve stimulation in female dogs

Contact Info

Product

Resources

About