INTRODUCTION:Erectile dysfunction (ED) impacts on both members of the couple. Female partners of men with ED are more likely to report reduced sexual quality of life than women whose partners do not have ED.AIM:To assess vardenafil efficacy in men with ED and determine the effects of treatment on their female partner's sexual quality of life.METHODS:Study participants comprised men aged 18-64 years with ED and their female partners. Eligible men had ED of ≥6 months' duration and a female partner who was motivated to support their ED treatment. Eligible women had a total Female Sexual Function Index score >23.55, indicating absence of significant sexual dysfunction. Following a 4-week screening period, men were randomized to treatment with vardenafil 10 mg or placebo, which could be titrated to 20 or 5 mg after 4 weeks.MAIN OUTCOMES MEASURES:Primary efficacy variables were question 3 of the Sexual Encounter Profile questionnaire (SEP3) and the quality-of-life domain of the modified Sexual Life Quality Questionnaire (mSLQQ-QOL).RESULTS:The intent-to-treat population included 343 couples, with 168 and 175 men receiving vardenafil or placebo, respectively. Vardenafil treatment significantly improved both erection maintenance and the female partners' sexual quality of life. Least squares (LS) mean SEP3 overall success rates after 12 weeks of treatment were 9.5 (baseline) vs. 67.2 (week 12) and 12.4 (baseline) vs. 24.2 (week 12) in the vardenafil and placebo groups, respectively (P < 0.0001). In female partners, LS mean mSLQQ-QOL scores were 28.8 (baseline) vs. 68.2 (last observation carried forward [LOCF]) in the vardenafil group and 24.6 (baseline) vs. 40.5 (LOCF) in the placebo group (P < 0.0001).CONCLUSIONS:Vardenafil treatment of men with ED improved both their erectile function and the sexual quality of life of their female partners.

INTRODUCTION:Men with erectile dysfunction (ED) are also likely to have associated underlying conditions.AIM:This retrospective analysis evaluated the efficacy and safety of vardenafil in men with ED and underlying conditions, including those taking concomitant medications.METHODS:A total of 13 randomized, double-blind, placebo-controlled clinical studies were included. Vardenafil was administered at a starting dose of 10 mg, adjustable to 5 or 20 mg after 4 weeks. Efficacy analyses were performed on the intent-to-treat (ITT) population, using a last observation carried forward approach. Efficacy was assessed for subgroups of patients with diabetes, hypertension, dyslipidemia, or metabolic syndrome (as defined by International Diabetes Federation criteria). Incidence rates of treatment-emergent adverse events were analyzed overall and by subgroup for patients in the safety population.MAIN OUTCOME MEASURES:Primary efficacy measures were the erectile function domain of the International Index of Erectile Function (IIEF-EF), and Sexual Encounter Profile questions 2 and 3 (SEP2, SEP3).RESULTS:In total, 4,326 patients were randomized to treatment; the ITT population included 4,143 patients, with 4,266 patients valid for safety. At 12 weeks, vardenafil therapy was associated with statistically significant improvements from baseline in IIEF-EF scores, and SEP2 and SEP3 success rates, including patients with ED and diabetes, hypertension, dyslipidemia, or metabolic syndrome. These improvements were irrespective of level of glycemic control, or use of concomitant medications for the treatment of diabetes, hypertension, or dyslipidemia. Across all subgroups, the number and type of treatment-emergent adverse events were consistent with results from previous studies of phosphodiesterase type 5 inhibitors in men with ED and underlying conditions.CONCLUSIONS:Vardenafil demonstrated favorable efficacy and tolerability in this large pool of patients with ED and underlying conditions. Importantly, the use of concomitant medications was not associated with any noteworthy changes in the efficacy or safety profile of vardenafil.

Aims: To assess if treatment with the alpha-glucosidase inhibitor acarbose can reduce cardiovascular events in type 2 diabetic patients.Methods and results: This meta-anatysis included seven randomized, double-blind, placebo-controlled acarbose studies with a minimum treatment duration of 52 weeks. Type 2 diabetic patients valid for safety were randomized to either acarbose (n=1 248) or placebo (n=932). The primary outcome measure was the time to develop a cardiovascular event. Primary analysis was conducted using Cox regression analysis. The effect of acarbose on metabolic parameters was also investigated. Acarbose therapy showed favourable trends towards risk reduction for all selected cardiovascular event categories. The treatment significantly reduced the risk for 'myocardial infarction' (hazards ratio=0. 36 [95% Cl 0.16-0.80], P=0.0120) and 'any cardiovascular event' (0.65 [95% Cl 0.48-0.88], P=0.0061). Glycaemic control, triglyceride levels, body weight and systolic blood pressure also improved significantly during acarbose treatment.Conclusion: Intervention with acarbose can prevent myocardial infarction and cardiovascular disease in type 2 diabetic patients white most of them are already on intensive concomitant cardiovascular medication. (C) 2003 Published by Elsevier Ltd on behalf of The European Society of Cardiology.

The effect of endothelin-1 (ET-1) on proliferation of aortic vascular smooth-muscle cells (VSMCs) from spontaneously hypertensive (SHRs) and normotensive Wistar-Kyoto (WKY) rats was assessed by the measurement of [3H]-thymidine incorporation into DNA. ET-1 stimulated DNA synthesis in a concentration-dependent manner. Half-maximal stimulation occurred at a concentration of 7 x 10(-11) M. Three separate administrations of ET-1 to the cell cultures resulted in a half-maximal stimulation at 3 x 10(-12) M in of VSCMs from SHRs. VSMCs from SHRs responded to a far greater extent compared with WKY rats. The stimulatory effect of ET-1 was significantly attenuated by atrial natriuretic peptide (ANP). Repeated administration of ANP led to exacerbation of the inhibitory effect. Serum-stimulated DNA synthesis was not influenced by ANP. The proliferative action of ET-1 and the inhibition by ANP are discussed with respect to the development of vascular disease in atherosclerosis and hypertension.

The role of endogenous atrial natriuretic peptide (ANP) in the immediate response of sodium excretion to unilateral nephrectomy (UNX) was investigated in anesthetized euvolemic rats through measurement of UNX-induced change in plasma ANP concentration and the response of the remaining kidney to UNX following administration of monoclonal anti-ANP antibodies. The circulating ANP levels almost tripled (from 23 +/- 4 to 66 +/- 13 fmol/ml, P < 0.01) within two minutes after UNX, whereas no change resulted from sham intervention. In the control group receiving vehicle injection, UNX resulted in a twofold increase in urinary sodium excretion (from 1.39 +/- 0.25 to 2.88 +/- 0.28 mumol/min, P < 0.01) related to a decrease in the fractional reabsorption of sodium at both proximal and distal sites (estimated from fractional excretion of lithium). Urinary excretion of cyclic guanosine 3'-5'-monophosphate (cGMP) increased as well, but glomerular filtration rate did not change. In addition, UNX was associated with a short-lived (< 20 min) rise in systemic arterial pressure and a transient fall in right atrial pressure. Administration of monoclonal anti-ANP antibodies totally prevented the UNX-associated natriuresis by blunting both proximal and distal tubular reabsorption of sodium, and suppressed the rise in urinary cGMP excretion following UNX. The duration of the post-UNX increase in arterial pressure was longer when compared to values observed in controls. These observations indicate that ANP release is stimulated after uninephrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the effects of continuous positive (CPAP) or negative airway pressure (CNAP) breathing (+/-10-12 cmH2O, duration 25 min) on blood content in the body's capacitance vasculature, regional distribution of labeled red blood cells was evaluated in seven spontaneously breathing supine volunteers. Counts were acquired by whole body scans and detectors overlying the liver, intestine, left ventricle, and lower arm, and arterial pressure, heart rate, calf blood flow and vascular resistance, hematocrit, vasopressin, and atrial natriuretic peptide plasma concentrations were also obtained. With CPAP, thoracic, cardiac, and left ventricular counts diminished significantly by 7-10%, were accompanied by significant increases in counts over both the gut and liver, and remained decreased during CPAP but reversed to baseline with zero airway pressure. Calf blood flow and vascular resistance significantly decreased and increased, respectively, whereas limb counts, arterial pressure, heart rate, and hormone concentrations remained unchanged. With CNAP, in contrast, regional counts and other variables did not change. Thus, moderate levels of CPAP deplete the intrathoracic vascular bed and heart, shifting blood toward the gut and liver but not toward the limbs. No short-term compensation increasing cardiac filling during CPAP was seen. In contrast, CNAP did not alter intrathoracic or organ blood content and, therefore, does not simply mirror the effects evoked by CPAP.

The authors evaluated in humans whether atrial natriuretic peptide (ANP) alters the regional distribution of blood in capacitance vessels. Eight healthy male volunteers (mean age: 30 years, range: 24–39) were studied twice. On different days and in a randomized, double blind fashion they received either αh-ANP (99–126), 25 μg intravenously followed by infusion of 0.1 μ kg−1 min−1, or vehicle. Changes of regional blood content in heart, liver, and intestine were evaluated at 3-min intervals using autologous radioactively (99mTc) labeled red cells. Calf circumference (strain gauge) central venous pressure, and heart rate were recorded continuously while arterial pressure (oscillometry), hematocrit, ANP and cGMP plasma concentrations were determined intermittently.

STUDY OBJECTIVE:Plasma levels of atrial natriuretic factor are increased in chronic heart failure; however, it is still controversial whether these raised levels contribute to the diuresis and natriuresis in this setting. To address this issue the potential contribution of endogenous atrial natriuretic factor in the renal excretion of a moderate oral sodium load in a rat model of chronic heart failure was studied.DESIGN:A monoclonal antibody against atrial natriuretic factor was used for specific antagonisation of its in vivo effects. Animals were subjected to oral sodium loading (30 ml.kg-1 0.9% NaCl, 2.5% dextrose) at baseline, immediately after, and 5 d after injection of monoclonal antibody or control solvent.EXPERIMENTAL MATERIAL:Sham operated rats and rats with chronic heart failure due to myocardial infarction (infarct size 35(SEM 4)% of left ventricle) were studied 4-5 weeks after surgery.MEASUREMENTS AND MAIN RESULTS:The renal excretion of cyclic guanosine monophosphate (cGMP), which represents a specific marker for the activation of the atrial natriuretic factor system, was markedly increased in infarcted rats, at 17.9(SEM 3.4) vs 5.8(1.2) nmol.kg-1, p less than 0.01. Atrial natriuretic factor antibody given immediately before sodium loading reduced the natriuretic response (0-4 h period) in infarcted rats from 1270(171) to 805(76) mumol.kg-1 (p less than 0.01) but not in sham operated animals. Similarly, the excretion of cGMP was only decreased by atrial natriuretic factor antibody in infarcted rats, from 29.8(6.3) to 20.7(3.7) nmol.kg-1. The reduction in sodium and cGMP excretion in infarcted rats was confirmed with a purified antibody preparation.CONCLUSIONS:Endogenous atrial natriuretic factor appears to be involved in the natriuresis following a moderate oral volume load in chronic heart failure. Thus the raised concentrations found in chronic heart failure may contribute to the regulation of urinary sodium excretion under these conditions despite the fact that the diuretic effects of exogenous atrial natriuretic factor are attenuated in chronic heart failure.