AT(1) receptor participates in the cardiac hypertrophy induced by resistance training in rats

Resistance training is accompanied by cardiac hypertrophy, but the role of the renin-angiotensin system (RAS) in this response is elusive. We evaluated this question in 36 male Wistar rats divided into six groups: control (n = 6); trained (n = 6); control + losartan (10 mg.kg(-1).day(-1), n = 6); trained + losartan (n = 6); control + high-salt diet (1%, n = 6); and trained + high-salt diet (1%, n = 6). High salt was used to inhibit the systemic RAS and losartan to block the AT(1) receptor. The exercise protocol consisted of: 4 x 12 bouts, 5x/wk during 8 wk, with 65-75% of one repetition maximum. Left ventricle weight-to-body weight ratio increased only in trained and trained + high-salt diet groups (8.5% and 10.6%, P < 0.05) compared with control. Also, none of the pathological cardiac hypertrophy markers, atrial natriuretic peptide, and alpha MHC (alpha-myosin heavy chain)-to-beta MHC ratio, were changed. ACE activity was analyzed by fluorometric assay (systemic and cardiac) and plasma renin activity (PRA) by RIA and remained unchanged upon resistance training, whereas PRA decreased significantly with the high-salt diet. Interestingly, using Western blot analysis and RT-PRC, no changes were observed in cardiac AT(2) receptor levels, whereas the AT(1) receptor gene (56%, P < 0.05) and protein (31%, P < 0.05) expressions were upregulated in the trained group. Also, cardiac ANG II concentration evaluated by ELISA remained unchanged (23.27 +/- 2.4 vs. 22.01 +/- 0.8 pg/mg, P > 0.05). Administration of a subhypotensive dose of losartan prevented left ventricle hypertrophy in response to the resistance training. Altogether, we provide evidence that resistance training-induced cardiac hypertrophy is accompanied by induction of AT(1) receptor expression with no changes in cardiac ANG II, which suggests a local activation of the RAS consistent with the hypertrophic response.

Long-term outcomes of radical cystectomy with preservation of prostatic capsule

We report our results of orthotopic ileal neobladder after radical cystectomy with prostatic adenomectomy with regard to urinary continence, sexual outcome and disease control. Between March 2003 and July 2004, 22 men with bladder transitional cell carcinoma (mean age 65.0) were analyzed. They underwent radical cystectomy with prostatic adenomectomy with preservation of the prostatic capsule, seminal vesicles and orthotopic ileal neobladder. Urinary continence was assessed after 2 days, 2 months, 6 months and 1 year. Preservation of sexual function was defined as the ability to have sexual intercourse and was assessed after 2-, 6-, and 12-months postoperatively. Overall survival and cancer-specific survival were assessed. Median postoperative follow-up was 60 months. Daytime and nighttime urinary continence after 48 h was 47 and 14%, respectively. After 2, 6 and 12 months, these rates were 74 and 16%, 85 and 26%, and 94 and 31%, respectively. Sexual intercourse was achieved in 69% of patients. Overall survival rate was 68%, and cancer-specific survival rate was 73%. Overall survival rates according to pathologic stage for pT0, pT1, pT2 and pT3 were 100, 60, 71 and 57%, and cancer-specific survival were 100, 80, 71 and 57%, respectively. Urinary continence and sexual function achieved by radical cystectomy with prostatic adenomectomy with orthotopic ileal neobladder seem to be similar to those achieved by the conventional technique with satisfactory oncologic results.

Salt-Induced Cardiac Hypertrophy and Interstitial Fibrosis Are Due to a Blood Pressure-Independent Mechanism in Wistar Rats

High salt intake is a known cardiovascular risk factor and is associated with cardiac alterations. To better understand this effect, male Wistar rats were fed a normal (NSD: 1.3% NaCl), high 4 (HSD4: 4%), or high 8 (HSD8: 8%) salt diet from weaning until 18 wk of age. The HSD8 group was subdivided into HSD8, HSD8+HZ (15 mg.kg(-1).d(-1) hydralazine in the drinking water), and HSD8+LOS (20 mg.kg(-1).d(-1) losartan in the drinking water) groups. The cardiomyocyte diameter was greater in the HSD4 and HSD8 groups than in the HSD8+LOS and NSD groups. Interstitial fibrosis was greater in the HSD4 and HSD8 groups than in the HSD8+HZ and NSD groups. Hydralazine prevented high blood pressure (BP) and fibrosis, but not cardiomyocyte hypertrophy. Losartan prevented high BP and cardiomyocyte hypertrophy, but not fibrosis. Angiotensin II type 1 receptor (AT(1)) protein expression in both ventricles was greater in the HSD8 group than in the NSD group. Losartan, but not hydralazine, prevented this effect. Compared with the NSD group, the binding of an AT(1) conformation-specific antibody that recognizes the activated form of the receptor was lower in both ventricles in all other groups. Losartan further lowered the binding of the anti-AT(1) antibody in both ventricles compared with all other experimental groups. Angiotensin II was greater in both ventricles in all groups compared with the NSD group. Myocardial structural alterations in response to HSD are independent of the effect on BP. Salt-induced cardiomyocyte hypertrophy and interstitial fibrosis possibly are due to different mechanisms. Evidence from the present study suggests that salt-induced AT(1) receptor internalization is probably due to angiotensin II binding. J. Nutr. 140: 1742-1751, 2010.

Local renin-angiotensin system regulates left ventricular hypertrophy induced by swimming training independent of circulating renin: a pharmacological study

Introduction. This study addressed the role of the local renin-angiotensin system (RAS) in the left ventriular hypertropy (LVH) induced by swimming training using pharmacological blockade. Materials and methods. Female Wistar rats treated with enalapril maleate (60 mg.kg(-1).d(-1), n = 38), losartan (20 mg.kg(-1).d(-1), n = 36) or high salt diet (1% NaCl, n = 38) were trained by two protocols (T1: 60-min swimming session, 5 days per week for 10 weeks and T2: the same T1 protocol until the 8(th) week, then 9(th) week they trained twice a day and 10(th) week they trained three times a day). Salt loading prevented activation of the systemic RAS. Haemodynamic parameters, soleus citrate synthase (SCS) activity and LVH (left ventricular/body weight ratio, mg/g) were evaluated. Results. Resting heart rate decreased in all trained groups. SCS activity increased 41% and 106% in T1 and T2 groups, respectively. LVH was 20% and 30% in T1 and T2 groups, respectively. Enalapril prevented 39% of the LVH in T2 group (p < 0.05). Losartan prevented 41% in T1 and 50% in T2 (P < 0.05) of the LVH in trained groups. Plasma renin activity (PRA) was inhibited in all salt groups and it was increased in T2 group. Conclusions. These data provide evidence that the physiological LVH induced by swimming training is regulated by local RAS independent from the systemic, because the hypertrophic response was maintained even when PRA was inhibited by chronic salt loading. However, other systems can contribute to this process.

Exercise training prevents beta-adrenergic hyperactivity-induced myocardial hypertrophy and lesions

Background: Sustained beta-adrenoreceptor activation promotes cardiac hypertrophy and cellular injury. Aims: To evaluate the cardioprotective effect of exercise on damage induced by beta-adrenergic hyperactivity. Methods: Male Wistar rats were randomised into four groups (n=8 per group): sedentary non-treated control (C), sedentary treated with isoproterenol 0.3 mg/kg/day administered subcutaneously for 8 days (1), exercised non-treated (E) and exercised plus isoproterenol administered during the last eight days of exercise (IE). Exercised animals ran on a treadmill for 1 h daily 6 times a week for 13 weeks. Results: Isoproterenol caused increases in left ventricle (LV) wet and dry weight/body weight ratio, LV water content and cardiomyocyte transverse diameter. Additionally, isoproterenol induced severe cellular lesions, necrosis, and apoptosis, increased collagen content and reduced capillary and fibre fractional areas. Notably, all of these abnormalities were completely prevented by exercise. Conclusion: Our data have demonstrated that complete cardioprotection is possible through exercise training; by preventing p-adrenergic hyperactivity-induced cardiac hypertrophy and structural injury. (c) 2008 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

OXIDATIVE STRESS BIOMARKER RESPONSES TO AN ACUTE SESSION OF HYPERTROPHY-RESISTANCE TRADITIONAL INTERVAL TRAINING AND CIRCUIT TRAINING

Deminice, R, Sicchieri, T, Mialich, MS, Milani, F, Ovidio, PP, and Jordao, AA. Oxidative stress biomarker responses to an acute session of hypertrophy-resistance traditional interval training and circuit training. J Strength Cond Res 25(3): 798-804, 2011-We have studied circuit resistance schemes with high loads as a time-effective alternative to hypertrophy-traditional resistance training. However, the oxidative stress biomarker responses to high-load circuit training are unknown. The aim of the present study was to compare oxidative stress biomarker response with an acute session of hypertrophy-resistance circuit training and traditional interval training. A week after the 1 repetition maximum (1RM) test, 11 healthy and well-trained male participants completed hypertrophy-resistance acute sessions of traditional interval training (3 x 10 repetitions at 75% of the 1RM, with 90-second passive rest) and circuit training (3 x 10 repetitions at 75% of the 1RM, in alternating performance of 2 exercises with different muscle groups) in a randomized and cross-over design. Venous blood samples were collected before (pre) and 10 minutes after (post) the resistance training sessions for oxidative stress biomarker assays. As expected, the time used to complete the circuit training (20.2 +/- 1.6) was half of that needed to complete the traditional interval training (40.3 +/- 1.8). Significant increases (p < 0.05) in thiobarbituric acid reactive substances (40%), creatine kinase (CK) (67%), glutathione (14%), and uric acid (25%) were detected posttraditional interval training session in relation to pre. In relation to circuit training, a significant increase in CK (33%) activity postsession in relation to pre was observed. Statistical analysis did not reveal any other change in the oxidative stress biomarker after circuit training. In conclusion, circuit resistance-hypertrophy training scheme proposed in the current study promoted lower oxidative stress biomarkers and antioxidant modulations compared with resistance traditional interval training.

Matrix metalloproteinase 9 gene haplotypes affect left ventricular hypertrophy in hypertensive patients

Background: Matrix metalloproteinases (MMPs) are involved in cardiac remodeling and are encoded by genes showing genetic polymorphisms that have functional implications. We examined whether MMP-9 genetic polymorphisms are associated with hypertension and with left ventricular (LV) remodeling in hypertensive patients. Methods: We studied 173 hypertensive patients and 137 age, race and gender matched healthy controls. Heart echocardiography was performed in all patients and the following MMP-9 genetic polymorphisms were analyzed: C-(1562)T (rs3918242). -90 (CA)(14-24) (rs2234681) and Q279R (rs17576). Haplo.stats analysis was used to assess whether MMP-9 haplotypes are associated with hypertension. Linear regression analysis was performed to assess whether MMP-9 haplotypes affect LV mass index (LVMI) and other echocardiography parameters. Results: MMP-9 90 (CA)14-24 ""HH"" genotype (H allele defined by number of CA repeats >= 21) was associated with hypertension (P = 0.0085; OR = 2.321, 95% confidence interval = 1.250 to 4.309). While one MMP-9 haplotype (""C. H, Q"") protects against LVMI and end-diastolic diameter increases due to remodeling (P = 0.0490 and P = 0.0367), another MMP-9 haplotype apparently has detrimental effects over both parameters in hypertensive patients (""T, H. Q"", P = 0.0015 and P = 0.0057. respectively). Conclusion: Genetic polymorphisms in MMP-9 gene may modify the susceptibility of hypertensive patients to LV remodeling. Further studies are necessary to examine whether these polymorphisms affect clinical events in hypertensive patients. (C) 2010 Elsevier B.V. All rights reserved.

Hypertrophy and neuron loss: structural changes in sheep SCG induced by unilateral sympathectomy

Recently, superior cervical ganglionectomy has been performed to investigate a variety of scientific topics from regulation of intraocular pressure to suppression of lingual tumour growth. Despite these recent advances in our understanding of the functional mechanisms underlying superior cervical ganglion (SCG) growth and development after surgical ablation, there still exists a need for information concerning the quantitative nature of the relationships between the removed SCG and its remaining contralateral ganglion and between the remaining SCG and its modified innervation territory. To this end, using design-based stereological methods, we have investigated the structural changes induced by unilateral ganglionectomy in sheep at three distinct timepoints (2, 7 and 12 weeks) after surgery. The effects of time, and lateral (left-right) differences, were examined by two-way analyses of variance and paired t-tests. Following removal of the left SCG, the main findings were: (i) the remaining right SCG was bigger at shorter survival times, i.e. 74% at 2 weeks, 55% at 7 weeks and no increase by 12 weeks, (ii) by 7 weeks after surgery, the right SCG contained fewer neurons (no decrease at 2 weeks, 6% fewer by 7 weeks and 17% fewer by 12 weeks) and (iii) by 7 weeks, right SCG neurons were also larger and the magnitude of this increase grew substantially with time (no rise at 2 weeks, 77% by 7 weeks and 215% by 12 weeks). Interaction effects between time and ganglionectomy-induced changes were significant for SCG volume and mean perikaryal volume. These findings show that unilateral superior cervical ganglionectomy has profound effects on the contralateral ganglion. For future investigations, it would be interesting to examine the interaction between SCGs and their innervation targets after ganglionectomy. Is the ganglionectomy-induced imbalance between the sizes of innervation territories the milieu in which morphoquantitative changes, particularly changes in perikaryal volume and neuron number, occur? Mechanistically, how would those changes arise? Are there any grounds for believing in a ganglionectomy-triggered SCG cross-innervation and neuroplasticity? (C) 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

Present and future pharmacotherapy for benign prostatic hyperplasia

Around 50% of men 51-60 years of age have pathological benign prostatic hyperplasia (BPH). Pharmacotherapy for BPH includes the 5alpha-reductase inhibitor finasteride, and alpha(1)-adrenoceptor antagonists. Finasteride reduces prostate volume and symptom scores, while increasing peak urinary flow rates. The main problem with finasteride treatment is that it increases the incidence of ejaculation disorders. All of the alpha(1)-adrenoceptor antagonists have been shown to reduce symptom scores and increase peak urinary flow rates in BPH. The nonselective alpha(1)-adrenoceptor antagonists (prazosin, terazosin and doxazosin) were developed as antihypertensives, and hypotensive-related side effects are the main problem with these agents in BPH. These side effects can be diminished by reducing peak concentrations of the drugs, as with once-daily alfuzosin, or by using the uroselective antagonist tamsulosin. Phytopharmaceuticals are commonly used in the treatment of BPH, such as saw palmetto berry which has been shown to improve the symptoms and peak urinary flow rate. Androgen receptor antagonists are not used in BPH because of their adverse effects. Newer drugs under development for the treatment of BPH include alpha(1)-adrenoceptor antagonists that show more selectivity for alpha(1A)-adrenoceptors than tamsulosin, combined 5alpha-reductase/alpha(1)-adrenoceptor inhibitors and combined type 1/type 2 5alpha-reductase inhibitors. New targets for the drug treatment of BPH include indothelin, growth factors, estrogens and the phosphodiesterase isoenzymes.

Abnormal left ventricular filling with increasing age reflects abnormal myocardial characteristics independent of ischemia or hypertrophy

Abnormal left ventricular (IV) filling may occur with increasing age despite apparently normal IV size and function, and is usually attributed to IV hypertrophy and coronary artery disease. The purpose of this study was to determine whether myocardial abnormalities could be identified in 67 such patients (36 men, mean age 57 +/- 9 years) whose IV hypertrophy and coronary artery disease were excluded by dobutamine echocardiography. All patients underwent gray scale and color tissue Doppler imaging from 3 apical views, which were stored and analyzed off line. Disturbances in structure and function were assessed by averaging the cyclic variation of integrated backscatter, strain rate, and peak systolic strain from each myocardial segment. Calibrated integrated backscatter (corrected for pericardial backscatter intensity) was measured in the septum and posterior wall from the parasternal long-axis view. Abnormal IV filling was present in 36 subjects (54%). Subjects with and without abnormal IV filling had similar IV mass, but differed in age (p <0.01), cyclic variation (p = 0.001), strain rate (p <0.01), and peak systolic strain (p <0.001). Multivariate logistic regression analysis demonstrated that age (p = 0.016) and cyclic variation (p = 0.042) were the most important determinants of abnormal IV filling in these apparently normal subjects. (C) 2003 by Excerpta Medica, Inc.

Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factors and cardioadrenergic activity. The aim of the present study was to determine if sympathetic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt treatment was initiated in rats seven days after uninephrectomy and contralateral renal denervation or sham renal denervation. DOCA (15 mg/kg, sc) or vehicle (soybean oil, 0.25 ml per animal) was administered twice a week for two weeks. Rats treated with DOCA or vehicle (control) were provided drinking water containing 1% NaCl and 0.03% KCl. At the end of the treatment period, mean arterial pressure (MAP) and heart rate measurements were made in conscious animals. Under ether anesthesia, the heart was removed and the right and left ventricles (including the septum) were separated and weighed. DOCA-salt treatment produced a significant increase in left ventricular weight/body weight (LVW/BW) ratio (2.44 ± 0.09 mg/g) and right ventricular weight/body weight (RVW/BW) ratio (0.53 ± 0.01 mg/g) compared to control (1.92 ± 0.04 and 0.48 ± 0.01 mg/g, respectively) rats. MAP was significantly higher (39%) in DOCA-salt rats. Renal denervation prevented (P>0.05) the development of hypertension in DOCA-salt rats but did not prevent the increase in LVW/BW (2.27 ± 0.03 mg/g) and RVW/BW (0.52 ± 0.01 mg/g). We have shown that the increase in arterial pressure level is not responsible for cardiac hypertrophy, which may be more related to other events associated with DOCA-salt hypertension, such as an increase in cardiac sympathetic activity.

Prostatic Arterial Supply: Anatomic and Imaging Findings Relevant for Selective Arterial Embolization

PURPOSE: To describe the anatomy and imaging findings of the prostatic arteries (PAs) on multirow-detector pelvic computed tomographic (CT) angiography and digital subtraction angiography (DSA) before embolization for symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: In a retrospective study from May 2010 to June 2011, 75 men (150 pelvic sides) underwent pelvic CT angiography and selective pelvic DSA before PA embolization for BPH. Each pelvic side was evaluated regarding the number of independent PAs and their origin, trajectory, termination, and anastomoses with adjacent arteries. RESULTS: A total of 57% of pelvic sides (n = 86) had only one PA, and 43% (n = 64) had two independent PAs identified (mean PA diameter, 1.6 mm ± 0.3). PAs originated from the internal pudendal artery in 34.1% of pelvic sides (n = 73), from a common trunk with the superior vesical artery in 20.1% (n = 43), from the anterior common gluteal-pudendal trunk in 17.8% (n = 38), from the obturator artery in 12.6% (n = 27), and from a common trunk with rectal branches in 8.4% (n = 18). In 57% of pelvic sides (n = 86), anastomoses to adjacent arteries were documented. There were 30 pelvic sides (20%) with accessory pudendal arteries in close relationship with the PAs. No correlations were found between PA diameter and patient age, prostate volume, or prostate-specific antigen values on multivariate analysis with logistic regression. CONCLUSIONS: PAs have highly variable origins between the left and right sides and between patients, and most frequently arise from the internal pudendal artery.

Prostatic Artery Embolization in the Treatment of Benign Prostatic Hyperplasia: Short and Medium Follow-Up

To evaluate the short and mid-term results of prostatic artery embolization in patients with benign prostatic embolization. Retrospective study between March 2009 and June 2011 with 103 patients (mean age 66.8 years, 50-85) that met our inclusion criteria with symptomatic benign prostatic hyperplasia. The clinical outcome was evaluated by the International Prostate Symptom Score (IPSS), quality of life (QoL), International Index of Erectile Function, prostate volume (PV), prostate-specific antigen (PSA), peak urinary flow (Q(max)), and post-void residual volume (PVR) measurements at 3 and 6 months, 1 year, 18 months, and 2 years after PAE and comparison with baseline values was made. Technical and clinical successes, as well as poor clinical outcome definitions, were previously defined. In this review, we evaluate the short and mid-term clinical outcomes and morbidity of patients treated only with non-spherical polyvinyl alcohol. Six months after the procedure, the PV decreased about 23%, IPSS changed to a mean value of 11.95 (almost 50% reduction), the QoL improved slightly more than 2 points, the Q(max) changed to a mean value of 12.63mL/s, the PVR underwent a change of almost half of the baseline value, and the PSA decreased about 2.3ng/mL. In the mid-term follow-up and comparing to the baseline values, we still assisted to a reduction in PV, IPSS, QoL, PVR, and PSA, and an increase in Q(max). Prostatic Artery Embolization is a safe procedure with low morbidity that shows good short- and mid-term clinical outcome in our institution.

Unilateral Versus Bilateral Prostatic Arterial Embolization for Lower Urinary Tract Symptoms in Patients with Prostate Enlargement

PURPOSE: This study was designed to compare baseline data and clinical outcome between patients with prostate enlargement/benign prostatic hyperplasia (PE/BPH) who underwent unilateral and bilateral prostatic arterial embolization (PAE) for the relief of lower urinary tract symptoms (LUTS). METHODS: This single-center, ambispective cohort study compared 122 consecutive patients (mean age 66.7 years) with unilateral versus bilateral PAE from March 2009 to December 2011. Selective PAE was performed with 100- and 200-μm nonspherical polyvinyl alcohol (PVA) particles by a unilateral femoral approach. RESULTS: Bilateral PAE was performed in 103 (84.4 %) patients (group A). The remaining 19 (15.6 %) patients underwent unilateral PAE (group B). Mean follow-up time was 6.7 months in group A and 7.3 months in group B. Mean prostate volume, PSA, International prostate symptom score/quality of life (IPSS/QoL) and post-void residual volume (PVR) reduction, and peak flow rate (Qmax) improvement were 19.4 mL, 1.68 ng/mL, 11.8/2.0 points, 32.9 mL, and 3.9 mL/s in group A and 11.5 mL, 1.98 ng/mL, 8.9/1.4 points, 53.8 mL, and 4.58 mL/s in group B. Poor clinical outcome was observed in 24.3 % of patients from group A and 47.4 % from group B (p = 0.04). CONCLUSIONS: PAE is a safe and effective technique that can induce 48 % improvement in the IPSS score and a prostate volume reduction of 19 %, with good clinical outcome in up to 75 % of treated patients. Bilateral PAE seems to lead to better clinical results; however, up to 50 % of patients after unilateral PAE may have a good clinical outcome.

Embolisation of Prostatic Arteries as Treatment of Moderate to Severe Lower Urinary Symptoms (LUTS) Secondary to Benign Hyperplasia: Results of Short- and Mid-Term Follow-Up

OBJECTIVES: To evaluate the short- and medium-term results of prostatic arterial embolisation (PAE) for benign prostatic hyperplasia (BPH). METHODS: This was a prospective non-randomised study including 255 patients diagnosed with BPH and moderate to severe lower urinary tract symptoms after failure of medical treatment for at least 6 months. The patients underwent PAE between March 2009 and April 2012. Technical success is when selective prostatic arterial embolisation is completed in at least one pelvic side. Clinical success was defined as improving symptoms and quality of life. Evaluation was performed before PAE and at 1, 3, 6 and every 6 months thereafter with the International Prostate Symptom Score (IPSS), quality of life (QoL), International Index of Erectile Function (IIEF), uroflowmetry, prostatic specific antigen (PSA) and volume. Non-spherical polyvinyl alcohol particles were used. RESULTS: PAE was technically successful in 250 patients (97.9 %). Mean follow-up, in 238 patients, was 10 months (range 1-36). Cumulative rates of clinical success were 81.9 %, 80.7 %, 77.9 %, 75.2 %, 72.0 %, 72.0 %, 72.0 % and 72.0 % at 1, 3, 6, 12, 18, 24, 30 and 36 months, respectively. There was one major complication. CONCLUSIONS: PAE is a procedure with good results for BPH patients with moderate to severe LUTS after failure of medical therapy. KEY POINTS: • Prostatic artery embolisation offers minimally invasive therapy for benign prostatic hyperplasia. • Prostatic artery embolisation is a challenging procedure because of vascular anatomical variations. • PAE is a promising new technique that has shown good results.