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      Different Effect of Losartan and Amlodipine on Penile Structures in Male Spontaneously Hypertensive Rats

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          Abstract

          Background: Erectile dysfunction is highly prevalent in hypertensive patients. Since both angiotensin II receptor type-1 blockers (ARBs) and calcium antagonists are current and effective antihypertensive drugs, the aim of this study was to determine possible differences between ARBs and calcium antagonists concerning the protection of penile structures from the deleterious effects of arterial hypertension. Methods and Results: During 6 months, 3 groups of male spontaneously hypertensive rats (SHR) and 1 of Wistar-Kyoto (WKY) rats, as a control group, were studied: SHR without treatment; SHR with losartan (L) 30 mg/kg/day; SHR with amlodipine (A) 3 mg/kg/day, and WKY without treatment. Cavernous smooth muscle (CSM) and vascular smooth muscle (VSM) from cavernous arteries, cavernous tissue fibrosis and collagen type III (COL III) were evaluated. After 6 months, SHR+L and SHR+A showed a similar reduction in blood pressure compared with untreated SHR. However, only SHR+L and control WKY presented significantly lower values of: CSM (p < 0.01), VSM (p < 0.01), and COL III ( p < 0.01) when compared with either untreated SHR or SHR+A. There was also a positive correlation between left ventricular mass and proteinuria with VSM from cavernous arteries, CSM and COL III in untreated SHR and SHR+A. These relations were not present in SHR+L and WKY. Conclusion: Although losartan and amlodipine achieved similar blood pressure control, losartan but not amlodipine showed a significant protective role against structural changes in the vessels and cavernous spaces of the erectile tissue caused by arterial hypertension.

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          Hypertension is associated with severe erectile dysfunction.

          M Burchardt, T Burchardt, L Baer … (2000)
          The prevalence and severity of erectile dysfunction in patients with hypertension need to be further evaluated. We evaluate medical and hypertension status, and erectile function in patients with hypertension. The International Index of Erectile Function, which is a detailed questionnaire, including well established components to evaluate patient medical history, hypertension status and erectile dysfunction, was mailed to 476 male patients of the outpatient Hypertension Center of Columbia Presbyterian Medical Center. The questionnaire was completed by 104 (22.3%) patients, and mean age was 62.2 years (range 34 to 75). Of the patients 84.8% were sexually active and 68. 3% had various degrees of erectile dysfunction, which was mild in 7. 7%, moderate in 15.4% and severe in 45.2%. Compared to the general population of erectile dysfunction cases in the literature our study population with hypertension had a higher incidence of severe erectile dysfunction. Although correlations of antihypertensive medications with incidence of erectile dysfunction did not reach statistical significance, there was a clear trend with patients treated with diuretics and beta-blockers having the highest incidence and those treated with alpha-blockers having the lowest incidence of erectile dysfunction. In addition to the observation that erectile dysfunction is more prevalent in patients with hypertension than in an age matched general population, our study shows that it is more severe in those with hypertension than in the general population.
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            Ca2+ channel blockers modulate metabolism of collagens within the extracellular matrix.

            O. Eickelberg, Erin Kohler, P Erne … (1996)
            The extracellular matrix (ECM) is an intricate network composed of an array of macromolecules capable of regulating the functional responsiveness of cells. Its composition greatly varies among different types of tissue, and dysregulation of its metabolism may contribute to vascular remodeling during the pathogenesis of various diseases, including atherosclerosis. In view of their antiatherosclerotic effects, the role of Ca2+ channel blockers in the metabolism of ECM was examined. Nanomolar concentrations of the five Ca2+ channel blockers amlodipine, felodipine, manidipine, verapamil, or diltiazem significantly decreased both the constitutive and platelet-derived growth factor BB-dependent collagen deposition in the ECM formed by human vascular smooth muscle cells and fibroblasts. The drugs inhibited the expression of fibrillar collagens type I and III and of basement membrane type IV collagen. Furthermore, Ca2+ channel blockers specifically increased the proteolytic activity of the 72-kDa type IV collagenase as shown by gelatin zymography and inhibited the transcription of tissue inhibitor of metalloproteinases-2.
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              Effect of antihypertensive treatment with valsartan or atenolol on sexual activity and plasma testosterone in hypertensive men.

              P Preti, Andrea C. Rinaldi, Amedeo Mugellini … (2002)
              To compare the effects of valsartan and atenolol on sexual activity and plasma testosterone in newly diagnosed, previously untreated, essential hypertensive male subjects. One hundred and ten hypertensive men, aged 40-49 years, homogeneous for marital status and without any previous sexual dysfunction were randomly treated with valsartan 80 mg daily (o.d.) or atenolol 50 mg o.d. for 16 weeks according to a double-blind, parallel-arm study design. After 8 weeks the dose was doubled in the non-responders (diastolic blood pressure > 90 mmHg). Clinical evaluation was performed after 8 weeks and 16 weeks of treatment and included blood pressure and plasma testosterone measurements and the compilation of a questionnaire about sexual activity (sexual intercourse episodes/month). Despite similar blood pressure lowering, atenolol significantly reduced sexual activity (from 6.0 sexual intercourse episodes/month to 4.2 sexual intercourse episodes/month, P < 0.01 vs placebo), whereas valsartan increased it, although not significantly (from 5.8 sexual intercourse episodes/month to 7.4 sexual intercourse episodes/month, P = 0.058), compared with placebo, but significantly compared with the atenolol group ( P < 0.05). Testosterone was reduced by atenolol (from 18.2 nmol/l to 13.8 nmol/l, P < 0.01 vs baseline) but was not affected by valsartan (from 17.6 nmol/l to 18.3 nmol/l). These results suggest that atenolol induces a worsening of sexual activity and a reduction of testosterone, whereas valsartan does not worsen sexual activity and does not change testosterone levels.
              Article 0 comments Cited 21 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (publisher-id): AJN
                Journal ID (nlm-ta): Am J Nephrol
                Journal ID (doi): 10.1159/issn.0250-8095
                Title: American Journal of Nephrology
                Publisher: S. Karger AG
                ISSN (Print): 0250-8095
                ISSN (Electronic): 1421-9670
                Publication date Subscription-year: 2004
                Publication date (Print): December 2004
                Publication date (Electronic): 28 February 2005
                Volume: 24
                Issue: 6
                Pages: 614-623
                Affiliations
                aLaboratory of Experimental Medicine, Hospital Alemán, and bInstituto de Investigaciones Cardiológicas, Buenos Aires, Argentina
                Article
                Publisher ID: 82598 Other ID: Am J Nephrol 2004;24:614–623
                DOI: 10.1159/000082598
                PubMed ID: 15591797
                SO-VID: e918336a-a791-4e68-9809-881f446a2369
                Copyright © © 2004 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 21 September 2004
                Date accepted : 05 November 2004
                Page count
                Figures: 8, Tables: 1, References: 29, Pages: 10
                Categories
                Subject: Original Report: Laboratory Investigation

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Angiotensin II receptor antagonists,Amlodipine,Spontaneously hypertensive rats,Erectile dysfunction,Corpus cavernous
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Angiotensin II receptor antagonists, Amlodipine, Spontaneously hypertensive rats, Erectile dysfunction, Corpus cavernous

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