Losartan Preserves Erectile Function After Bilateral Cavernous Nerve Injury via Antifibrotic Mechanisms in Male Rats

Cangüven, Önder; Lagoda, Gwen A.; Sezen, Sena F.; Burnett, Arthur L.

doi:10.1016/j.juro.2009.01.097

Cited by 49 publications

(40 citation statements)

References 19 publications

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“…Activation of Smad- and non-Smad-dependent TGF-β1 signaling pathways is believed to contribute to Ang II-induced apoptosis and tissue fibrosis [14, 15, 40, 43, 44]. It was previously reported that treatment with losartan suppressed the TGF-β1/Smad pathway and preserved erectile function [7, 21]. However, these results did not predict whether Ang II antagonism would attenuate apoptosis and fibrosis in the corpus cavernosum and severe CVOD.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, a recent study revealed that decreased erectile function was accompanied by TGF-β1/Smad pathway activation in the rat corpus cavernosum following bilateral cavernous nerve injury. Treatment with losartan, an antagonist of the Ang II type 1 receptor, suppressed the TGF-β1/Smad pathway and preserved erectile function, suggesting that Ang II type 1 receptor antagonism may counteract structural changes in the corpus cavernosum and preserve erectile function [21]. In addition, recent evidence indicates that blocking of Ang II is more important than inhibition of TGF-β in non-penile tissue fibrosis [22], and combined therapy with sildenafil and losartan presented a better outcome in terms of functional and structural modification in the cavernous tissue of spontaneously hypertensive rats (SHR) as compared with either of the two drugs alone [23].…”

Section: Introductionmentioning

confidence: 99%

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Losartan Preserves Erectile Function by Suppression of Apoptosis and Fibrosis of Corpus Cavernosum and Corporal Veno-Occlusive Dysfunction in Diabetic Rats

Zheng

et al. 2017

Cell Physiol Biochem

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Background/Aims: Transforming growth factor-β1 (TGF-β1) plays important roles in penile corporal fibrosis and veno-occlusive dysfunction (CVOD). Angiotensin II (Ang II) is critically involved in erectile dysfunction, and blocking of Ang II is more important than inhibition of TGF-β in non-penile tissue fibrosis. However, the role of Ang II in corporal fbrosis and CVOD in a diabetic condition has not been investigated. Methods: Diabetic rats were treated with sildenafil or losartan (an Ang II antagonist) alone or in combination. Intracavernosal pressure, dynamic infusion cavernosometry, and histological and molecular alterations of the corpus cavernosum were examined. Results: Diabetic rats exhibited decreases in erectile response, severe CVOD, apoptosis, fibrosis, and activation of the TGF-β1 pathway. Treatment with sildenafil had a modest effect on erectile response and an insignificant suppressive effect on CVOD, apoptosis, fibrosis, and the TGF-β1 pathway. Although losartan greatly improved the histological and molecular changes and CVOD as compared with sildenafil, its effect on erectile response was low. The combination of sildenafil and losartan had superior effects on these parameters than did either compound alone. Conclusion: Ang II activation may be involved in apoptosis and fibrosis of the corpus cavernosum through Smad and non-Smad pathways, resulting in CVOD and ED. The low efficacy of sildenafil in a diabetic ED rat model was at least partly due to its inadequate effects on apoptosis, fibrosis, and CVOD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Losartan Preserves Erectile Function by Suppression of Apoptosis and Fibrosis of Corpus Cavernosum and Corporal Veno-Occlusive Dysfunction in Diabetic Rats

Zheng

et al. 2017

Cell Physiol Biochem

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“…The same has been observed for hypertensive patients treated with valsartan; reduced ED and improved orgasmic function and sexual satisfaction (92). Also, it was found that losartan helps preserve erectile function in male rats after bilateral cavernous nerve injury by counter-acting fibrotic activator factors (93). However, recent study showed no change in ED progression in humans with ACEI or angioten-receptor blocker (ARB) therapy (94).…”

Section: Hypertension and Edmentioning

confidence: 76%

The Role Erectile Dysfunction Plays in Cardiovascular Diseases

Crestani¹,

Nunes²,

Marques³

et al. 2012

Erectile Dysfunction - Disease-Associated Mechanisms and Novel Insights Into Therapy

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“…The renin-angiotensin system (RAS) has an important role in the ED regarding the remodelling process (27). Angiotensin II, an active product of the RAS, induces various physiological action, vasoconstriction, and endothelial dysfunction via the increased production of reactive oxygen species (ROS) and eicosanoids (9). Angiotensin II contributes to the vascular remodeling in the penis, resulting in the hypertension-related ED.…”

mentioning

confidence: 99%

“…Also, hypertrophy of corpus cavernous smooth muscle and vascular smooth muscle has been confirmed in the SHR (32). In previous studies, the protective effect of ARB, such as losartan and candesartan, was already investigated in the penis in the SHR (9,25). Olmesartan medoxomil (olmesartan) is a newer ARB than losartan, and more effective to antagonize the AT1R (2).…”

mentioning

confidence: 99%

Effect of an angiotensin II receptor blocker and a calcium channel blocker on hypertension associated penile dysfunction in a rat model

et al. 2014

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Possible effect of olmesartan, an angiotensin II receptor blocker (ARB), or nifedipine, an L-type calcium channel blocker, on penile dysfunction in the spontaneously hypertensive rat (SHR) was investigated in this study. Twelve-week-old male SHRs were treated with olmesartan (1 or 3 mg/ kg, per orally (p.o.)) or nifedipine (30 mg/kg, p.o.) once a day for 6 weeks. Wistar rats and SHRs with vehicle treatment were used as controls. Penile cGMP and malondialdehyde concentrations, and mRNA levels of endothelial and neuronal NO synthase (eNOS and nNOS) were measured. Penile function was evaluated by organ bath studies with norepinephrine-induced contractions and acetylcholine-induced relaxations. The SHR showed significantly increased blood pressure, decreased cGMP concentrations, increased malondialdehyde concentrations, decreased eNOS and nNOS mRNA levels, norepinephrine-induced hyper-contractions, and acetylcholine-induced hyporelaxations in the penile tissue compared to the Wistar rat. Both nifedipine and olmesartan significantly decreased blood pressure, increased cGMP and normalized the hyper-contractions and hypo-relaxations observed in the SHR group. However, not nifedipine but olmesartan improved the malondialdehyde concentrations and increased mRNA levels of eNOS and nNOS in the penis. Our results indicate that the hypertension-associated penile dysfunction might be treated with ARBs such as olmesartan better than calcium channel blockers, such as nifedipine.Hypertension induces vascular remodeling, pathological changes in the penis, and subsequent diminished blood supply to the penile tissue. In addition, hypertension represents one of the major risk factors for the development of vasculogenic erectile dysfunction (ED) (16,28). ED frequently appears in hypertensive patients than in normotensive individuals (10). The extent of ED directly depends on the degree and time of hypertension (8). Clinical studies show that approximately 30% of hypertension patients have ED compared to 9.6% in the common population (12, 28). Thus, antihypertensive therapies in hypertension-related ED patients are necessary in order to reduce the blood pressure and further protect the cavernous tissue. However, some of these therapies did not always improve the symptoms of ED in hypertensive patients (22,23). In clinical studies, the older antihypertensive drugs, i.e., diuretics and β-adrenoreceptor blockers, may exert detrimental effect on ED. On the other hand, more recent drugs have neutral (calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors) or favorable (angiotensin II type 1 receptor (AT1R) blockers (ARBs)) effects (11,22). These data suggest that blood pressure control may not be the only treatment strategy to improve erec-

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Losartan Preserves Erectile Function After Bilateral Cavernous Nerve Injury via Antifibrotic Mechanisms in Male Rats

Cited by 49 publications

References 19 publications

Losartan Preserves Erectile Function by Suppression of Apoptosis and Fibrosis of Corpus Cavernosum and Corporal Veno-Occlusive Dysfunction in Diabetic Rats

Losartan Preserves Erectile Function by Suppression of Apoptosis and Fibrosis of Corpus Cavernosum and Corporal Veno-Occlusive Dysfunction in Diabetic Rats

The Role Erectile Dysfunction Plays in Cardiovascular Diseases

Effect of an angiotensin II receptor blocker and a calcium channel blocker on hypertension associated penile dysfunction in a rat model

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