The density and distribution of endothelin 1 and endothelin receptor subtypes in normal and diabetic rat corpus cavernosum

Bell, C.R.W.; Sullivan, M.; Dashwood, Michael R.; Muddle, J. R.; Morgan, Robert J.

doi:10.1111/j.1464-410x.1995.tb07675.x

Cited by 60 publications

(48 citation statements)

References 19 publications

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“…In the diabetic rat study referenced above, the authors were unable to detect any appreciable binding to the ETB receptor in CCSM from either normal or diabetic rats, 19 while the above rabbit study found a three-fold increase in ETB radioligand binding. 20 Recent pharmacologic evidence is consistent with the existence of two different populations of ETB receptors, activation of one causing smooth muscle relaxation (ETB1) and the other causing smooth muscle contraction (ETB2).…”

Section: Discussionmentioning

confidence: 83%

“…19 Using the same technique, this same group reported that ETB, but not ETA or ET-1, was significantly upregulated in diabetic rabbits. 20 In a separate study, they reported a decrease in ETB receptor binding sites in the cavernosal tissue of hypercholesterolemic rabbits.…”

Section: Introductionmentioning

confidence: 91%

“…18 Thus, the relative expression of these ET receptors may be crucial for defining the contractile state of the CCSM. Although both ETA and ETB receptors exist in mammalian CCSM 19 including human, 14 ET-1-induced CCSM contraction appears to be mediated predominantly by ETA receptors.…”

Section: Introductionmentioning

confidence: 99%

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Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase β

et al. 2003

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Corpus cavernosum smooth muscle (CCSM) from rabbits made diabetic for 6 months as a result of alloxan injection exhibited increased sensitivity (3vs 9 nM EC 50 ) and generated 20-50% greater force to endothelin-1 (ET-1) compared to CCSM from normal rabbits. In contrast, the force produced by the CCSM in response to KCl and phenylephrine was not significantly altered in diabetic CCSM. The increased ET-1 sensitivity is associated with a two to three-fold upregulation of ET receptor A at both mRNA and protein levels in diabetic CCSM. ET-1-induced CCSM contraction is largely dependent upon Rho-kinase (ROK), since it is almost completely blocked by Y-27632 (a highly selective ROK inhibitor). Furthermore, expression of ROKb isoform is selectively upregulated in CCSM from diabetic rabbits. Thus, an increased CCSM tone, modulated by sensitization of the endothelin-mediated contractile pathway via ROK, may be a key component of the molecular mechanism of diabetes-induced erectile dysfunction.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 91%

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Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase β

et al. 2003

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“…15,35 Additionally, increased plasma and corporal body endothelin levels have been seen in diabetic men with ED. 36,37 This appears to be important in the pathogenesis of ED, as ET-1 is a key factor in maintaining corpus cavernosal smooth muscle tone. 38,39 While not completely defined, manifestations of endothelial dysfunction may differ between type I and II DM.…”

Section: Diabetes Mellitusmentioning

confidence: 99%

Linking erectile dysfunction and coronary artery disease

2005

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Coronary artery disease (CAD) and erectile dysfunction (ED) are both highly prevalent conditions that frequently coexist. Additionally, they share mutual vascular risk factors, suggesting that they are both manifestations of systemic vascular disease. The role of endothelial dysfunction in CAD is well established. Normal erectile function is primarily a vascular event that relies heavily on endothelially derived, nitric oxide-induced vasodilation. Accordingly, endothelial dysfunction appears to be a common pathological etiology and mechanism of disease progression between CAD and ED. The risk factors of diabetes mellitus, hypertension, hyperlipidemia, obesity and tobacco abuse contribute to endothelial dysfunction. This article reviews the role of vascular endothelium in health, the abnormalities resulting from vascular risk factors, and clinical trials evaluating the role of endothelial dysfunction in ED.

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“…4 In the penis, ET-1 is a profibrotic peptide and the most potent stimulator of cavernosal contractility, acting on receptors identified in different animal species, including humans. [3][4][5][6][7][8][9] In human penile cells, ET-1 expression is upregulated by several factors such as transforming growth factor-b1 (TGF-b1), interleukin-1a, ET-1 itself and by prolonged (24 h) hypoxia. 4 Hypoxia is a normal, physiological event in the penis, which, in the flaccid state, resides at a very low oxygen tension (P O 2 ¼ 25-40 mm Hg).…”

Section: Introductionmentioning

confidence: 99%

Effect of sildenafil administration on penile hypoxia induced by cavernous neurotomy in the rat

et al. 2007

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Hypoxia is a normal, physiological condition in penile tissue, which is interrupted by reoxygenation associated to sleep-related erections. We previously described in the rat that a penile fibrosis and overexpression of the pro-fibrotic endothelin-1 type B receptor (ETB) are associated to prolonged (3 months) hypoxia induced by the bilateral surgical resection of the cavernous nerves (bilateral cavernous neurotomy (BCN)). The aim of the present study was to define the time frame in which BCN induces hypoxia and ETB overexpression in the penile tissue. In addition, we studied the timedependency of the rescuing effect of an acute administration of the phosphodiesterase type 5 inhibitor, sildenafil. We found that BCN induced penile hypo-oxygenation (immunohistochemistry for Hypoxyprobe), penile ETB mRNA overexpression (quantitative real-time reverse transcriptase polymerase chain reaction) and hypersensitivity to the ETB agonist IRL-1620 (in vitro contractility study). Sildenafil treatment was able to counteract all these alterations (penile hypoxygenation, hyper-sensitivity to IRL-1620 and ETB overexpression), with its effect being more evident the earlier it was administered.

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The density and distribution of endothelin 1 and endothelin receptor subtypes in normal and diabetic rat corpus cavernosum

Cited by 60 publications

References 19 publications

Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase β

Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase β

Linking erectile dysfunction and coronary artery disease

Effect of sildenafil administration on penile hypoxia induced by cavernous neurotomy in the rat

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