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Biomedical subjects

Edgardo Becher

Publications and source records attributed to Edgardo Becher.

4 recordsLinked to original sources
PubMed2006

Differences between Candesartan and Hydralazine in the protection of penile structures in spontaneously hypertensive rats.

INTRODUCTION: Previous studies indicate that angiotensin type I receptor antagonists present a beneficial effect on penile structures in hypertensive rats. However, at present there is no substantial information concerning the functional aspect of this class of antihypertensive drugs. AIM: To determine, by in vitro studies, functional effects of Candesartan in comparison with a traditional vasodilating agent, Hydralazine, on penile structures in a rat model of arterial hypertension. METHODS: During 4 months, three groups of male spontaneously hypertensive rats (SHR) and one of Wistar-Kyoto (WKY) rats, as control group, were studied: SHR without treatment; SHR with Candesartan cilexetil 7.5 mg/kg/day; SHR with Hydralazine 50 mg/kg/day; and WKY rats without treatment. Cavernous smooth muscle strips were mounted in an organ bath system for in vitro studies. In addition, cavernous smooth muscle and vascular smooth muscle from cavernous arteries, cavernous tissue fibrosis, and collagen type III were also evaluated by immunohistochemistry. RESULTS: After 4 months, SHR with Candesartan and Hydralazine showed similar reduction in blood pressure compared with untreated SHR. However, in vitro studies revealed that SHR with Candesartan displayed a better relaxation response to acetylcholine than SHR and SHR with Hydralazine (P < 0.01). Immunostaining indicates that only SHR with Candesartan and control WKY rats showed significantly lower values of: (i) cavernous smooth muscle (P < 0.01); (ii) vascular smooth muscle (P < 0.01); and (iii) collagen type III (P < 0.01) when compared with untreated SHR or SHR with Hydralazine. Additionally, SHR with Candesartan presented a higher endothelial nitric oxide synthase expression in sinusoidal endothelium in comparison with SHR, and SHR with Hydralazine (P < 0.01). CONCLUSION: Candesartan presented equivalent blood pressure control compared with Hydralazine. However, only Candesartan showed a significant better response to acetylcholine, in in vitro studies, with a protective role against structural changes in vessels as well as in cavernous spaces of the erectile tissue.

Analysis of Variance↗
PubMed2004

Pharmacotherapy for erectile dysfunction.

INTRODUCTION: Advances in understanding of the biochemistry and physiology of penile erection have led to breakthroughs in pharmacotherapy of erectile dysfunction. AIM: To provide recommendations/guidelines concerning state-of-the-art knowledge for the putative molecular and cellular mechanisms of action of centrally and peripherally acting drugs currently utilized in pharmacotherapy of erectile dysfunction. METHODS: An international consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a two-year period. Concerning the Pharmacotherapy for Erectile Dysfunction Committee there were 25 experts from 10 countries. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. RESULTS: Selective and potent oral PDE5 inhibitors have significantly more affinity than cGMP and form broader molecular interactions with multiple amino acids, thereby blocking access to cGMP in the catalytic sites of the PDE5 enzyme. PDE5 inhibitors, which vary as to biochemical potency, selectivity and pharmacokinetics, lead to cGMP elevation and relaxation facilitation of penile corpus cavernosum smooth muscle cells following sexual stimulation. Various centrally acting drugs influence sexual behaviour. In particular, the dopaminergic substance apomorphine is a central enhancer that acts in the paraventricular nucleus of the hypothalamus as a dopamine (D2) receptor agonist, induces and increases penile erection responses via disinhibition, following sexual stimulation. CONCLUSIONS: There is a need for more research in the pharmacotherapeutic development of central and peripheral agents for safe and effective erectile dysfunction treatment.

Apomorphine↗
PubMed2004

Topical alprostadil cream for the treatment of erectile dysfunction.

Erectile dysfunction (ED) has serious negative consequences on both sexual experience and emotional well being and affects a broad range of age groups. The prevalence of ED is associated with increasing age and has been reported to be as high as 70%. Although the disorder is common and underdiagnosed, its treatment can significantly improve patients' quality of life. Systemic treatment with oral phosphodiesterase type-5 (PDE-5) inhibitors is the current standard of care for patients with ED. Some patients, however, have absolute contraindications for PDE-5 inhibitors. In addition, these agents can be associated with adverse effects. Furthermore, because PDE-5 inhibitors are not as effective in patients who have undergone radical prostatectomy or who have severe vascular disease, a substantial unmet medical need exists among patients who have ED as a result of these conditions. Consequently, PDE-5 inhibitor therapy is associated with a high rate of discontinuation, as are intracavernosal or transurethral therapies, which are inconvenient and invasive. Several studies, including four double-blind, placebo-controlled, Phase II trials, show that alprostadil topical cream is efficacious and well-tolerated in ED in patients with mild-to-severe symptoms, in those undergoing treatment for cardiovascular diseases and diabetes and in otherwise healthy ED patients. Thus, alprostadil topical cream is a potential first-choice alternative for ED in patients who do not respond or who cannot tolerate or do not accept PDE-5 inhibitor therapy.

3',5'-Cyclic-GMP Phosphodiesterases↗