美托洛尔对青年男性高血压患者勃起功能的影响

目的:探讨美托洛尔对青年男性高血压患者勃起功能的影响。方法:调查门诊和住院的69名青年高血压患者使用美托洛尔50～150mg/d后性功能改变情况,以勃起功能国际问卷-5(IIEF-5)形式进行为期12个月以上的跟踪随访。结果:服用美托洛尔的青年男性高血压患者勃起功能障碍的发生率高达79.41%,治疗3个月、6个月的发生率分别为36.76%和66.18%(P<0.01)。勃起功能障碍的程度与服用美托洛尔的疗程和剂量呈正相关。结论:青年男性高血压患者应用美托洛尔可引起勃起功能障碍。因此,对青年男性高血压患者应选择适当的降血压药并合理使用,以减少或避免药物性勃起功能障碍的发生。     

A comparative study of nebivolol and (S) atenolol on blood pressure and heart rate on essential hypertensive patients

Objectives:

To study the effect of nebivolol 5 mg once daily versus (S)-atenolol 25 mg once daily in patients with essential hypertension.

Materials and Methods:

A prospective study was conducted at RLJH and Research Centre which included 30 patients in each group with essential hypertension. The sex, age, presenting illness, and family history of the patients were recorded. Investigations such as blood sugar, urine analysis, kidney function test, lipid profile, and ECG were performed before starting the treatment. Any adverse effects during the treatment were noted. Blood pressure and heart rate were recorded at baseline and during follow-up. One group received nebivolol 5 mg once daily and other group (S)atenolol 25 mg once daily. Patients were followed-up every 15 days for 3 months.

Results:

Nebivolol group had 18 males and 12 females with mean age 50.6 ± 9.5 years, (S)-atenolol had 16 males and 14 females with mean age 54.4 ± 9 years. Patients receiving nebivolol and (S)-atenolol showed a significant fall (P <·0001) in systolic (SBP), diastolic blood pressure (DBP), and heart rate at the end of first, second, and third month when compared to baseline. The difference in fall in SBP and DBP was insignificant between the groups, but fall in heart rate was significant (P <·0001). Adverse effects such as headache, dizziness, and fatigue were reported with both drugs.

Conclusion:

Reduction of blood pressure with nebivolol and (S)atenolol was similar, but fall in blood pressure from baseline was highly significant in both groups.     

普萘洛尔和硝苯地平对男性高血压患者性功能影响

目的:探讨普萘洛尔和硝苯地平对男性高血压患者性功能的影响。方法:选取2008年1月-2011年1月在延安大学附属医院就诊的94例高血压患者作为研究对象,将所有对象随机分为2组,一组采用普萘洛尔治疗,一组采用硝苯地平治疗,观察治疗8周前后血压及性功能的改变。结果:2组患者在药物治疗8周后,血压水平较治疗前均明显降低(P<0.05);采用普萘洛尔治疗前后,患者性功能明显降低(P<0.05),而采用硝苯地平治疗前后,患者性功能无明显变化;普萘洛尔组在治疗后勃起功能障碍发生率明显高于硝苯地平组;普萘洛尔组在治疗后,机体内睾酮含量明显降低(P<0.05),而硝苯地平在治疗后无明显改变(P>0.05)。结论:普萘洛尔能影响患者的性功能,而硝苯地平不影响患者的性功能,因此对于高血压患者在采用降压治疗时,选择硝苯地平较好。     

美托洛尔对隐匿性肾功能不全的高血压患者肾小球滤过功能的影响

目的:评价β受体阻滞剂美托洛尔单独或与血管紧张素转换酶(ACE)抑制剂贝那普利联合应用对隐匿性肾功能不全的轻、中度高血压患者肾小球滤过功能的影响。方法:73例隐匿性肾功能不全的高血压患者,随机分为美托洛尔(MET)、美托洛尔+贝那普利(MET+BEN)两组,分别应用美托洛尔50～75mg/d或美托洛尔25mg/d+贝那普利5～10mg/d,疗程6个月。血压控制目标为140/90mmHg。治疗前和治疗满6个月时,检测两组患者血尿酸(SUA)血肌酐(Scr)和肾小球滤过率GFR。结果:①治疗后,MET组与MET+BEN组的血压平均水平的差别均无统计学意义(131.3±9.9/71.9±10.5,132.0±10.2/68.9±10.7mmHg,P均>0.05),血压控制达标率亦无显著差别(78.4%,77.8%,P>0.05)。②治疗后MET组血尿酸、肌酐较治疗前升高(439±62,429±57mmol/L,P<0.05;109±17,103±14μmol/L,P<0.01),肾小球滤过率轻度下降(49.9±6.9,52.9±5.8mL/min·1.73m2,P<0.01);③MET+BEN组血尿酸、血肌酐较治疗前降低(417±57,426±62mmol/L,P<0.01;98±12,105±13μmol/L,P<0.01),肾小球滤过率较治疗前升高(54.7±6.2,51.3±5.6mL/min·1.73m2,P<0.01)。④治疗6个月后,MET+BEN组血尿酸、血肌酐均低于MET组(417±57,439±62mmol/L,P<0.01;98±12,109±17μmol/L,P<0.01),肾小球滤过率高于MET组(54.7±6.2,49.9±6.9ml/min·1.73m2,P<0.01)。结论:对合并隐匿性肾功能不全的高血压患者,应避免单独应用美托洛尔,以免加重肾小球滤过功能的损害;而美托洛尔与贝那普利联合应用,可能有益于肾功能的保护。     

Time course of blood pressure,pulse rate,plasma renin and metoprolol during treatment of hypertensive patients

Summary Eleven patients were treated for essential hypertension with metoprolol (Selokén^®) for more than three months. The time course of changes in blood pressure, pulse rate and plasma renin activity was studied during treatment with an oral maintenance dose of 100 mg twice daily. Significant decreases in pulse rate, diastolic blood pressure and plasma renin activity were observed even after the first dose. The plasma concentration of metoprolol reached equilibrium after the second dose. After the third dose there was no further significant change in blood pressure. There was a significant correlation (p<0.001) between the initial (after three doses) and final (after >90days) effect of metoprolol on blood pressure (r=0.86 and 0.91 for systolic and diastolic blood pressure change, respectively).     

卡维地洛与美托洛尔对照治疗原发性高血压60例

目的:评价卡维地洛对原发性高血压的临床疗效及安全性.方法:60例原发性高血压患者经过2周安慰剂洗脱期后随机分为:对照组30例给予美托洛尔25mg,bid,服药2周末血压下降未达有效标准增至50mg,bid,疗程共8周.治疗组给予卡维地洛10mg,bid,服药2周末血压下降未达有效标准者增至20mg,bid,疗程共8周.结果:治疗组降压总有效率80.0%,显效率56.7%,对照组总有效率73.3%,显效率53.3%;两组疗效比较差异无显著性(P>0.05),不良反应发生率差异无显著性(P>0.05).不良反应程度轻微,可耐受.结论:卡维地洛是治疗原发性高血压的安全有效的药物.     

Cadralazine versus prazosin as second-step treatment in hypertensive patients on beta-blockers: a randomized multicentre study

Summary A randomized multicentre between-patient study comparison has been made of the efficacy and tolerability of cadralazine and prazosin, both administered for 6 weeks to hypertensive patients with a supine diastolic blood pressure (DBP) 95 mm Hg whilst on a beta-adrenoceptor-blocker. The doses of the beta-adrenoceptor-blocker (metoprolol SR 200 mg once daily) and cadralazine (10 mg once daily) were held constant during the study, while prazosin was individually titrated from 0.5 mg to a maximum of 2 mg tds.108 patients (50 m and 58 f; mean age 54 y) were enrolled in 12 centres. Twelve patients withdrew due to adverse effects or poor efficacy (5 patients on prazosin and 7 on cadralazine).Both treatments induced a similar significant reduction in systolic blood pressure (SBP) and DBP, allowing normalization of BP in 58% of subjects on cadralazine and 55% on prazosin. Heart Rate (hR) increased significantly from 67 to 72 beats · min^–1 in those on cadralazine and from 65 to 69 beats · min^–1 on prazosin. Body weight was unchanged.Adverse effects were mild and typical of vasodilators, such as headache, flushing and dizziness. Physician evaluation of drug efficacy was not different between drugs, and cadralazine was rated better in terms of tolerability.Thus, in this multicentre study, cadralazine in the fixed dose of 10 mg once daily, as a second-step antihypertensive treatment in patients not satisfactorily controlled by a beta-adrenoceptor-blocker, was as effective and showed a similar side effect profile to prazosin given three times daily.For the Italian Multicentre Study Group Participating Centres: C. Canale, V. Terrachini (Genova); G. Paoletti, A. Camerieri (Sestri Ponente); G. Gandolfi (La Spezia); A. Castelluccio, C. Mondelli (S. Remo); G. Maschio, V. Bedogna (Verona); A. Spedo (Badia Polesine); P. Cantù, A. Limido (Gallarate); F. Valentini (Como); G. Viglino (Alba); C. Martines, E. Casiglia (Piove di Sacco); R. Miori, M. Dalfollo (Trento); P. Maiolino, A. Carrozza (Cittadella)     

Effect of metoprolol and propranolol on platelet aggregation and cAMP level in hypertensive patients

Summary Ten patients with uncomplicated moderate essential hypertension were recruited to evaluate the effect of the non-selective beta-blocker propranolol and the beta₁-selective beta-blocker metoprolol on platelet aggregation and cAMP formation. Five patients began treatment with propranolol 80 mg b. i. d. and 5 with metoprolol 100 mg b. i. d., and after 2 weeks the treatments were exchanged. ADP- and adrenaline-induced platelet aggregation and the basal level of platelet cAMP were measured at the end of each treatment period. Platelet aggregation was tested turbidometrically, using the threshold value for irreversible aggregation, and cAMP measurements were performed using a protein-binding assay.Both ADP and adrenaline thrshold values were significantly lower after propranolol than after metoprolol.The basal cAMP level was lower during propranolol than metoprolol treatment.The results indicate that platelet aggregation and basal cAMP level are influenced by beta-blockers in proportion to their affinity to different beta-adrenoceptors. This may be of value in the beta-blocker treatment of patients at high thrombotic risk.     

Effects of treatment with nifedipine and metoprolol in essential hypertension

Summary In a double-blind trial 26 patients with essential hypertension were treated with nifedipine or placebo for 8 weeks, following a 4-week run-in place-bo period in all patients. The daily dosage of nifedipine during this phase was 10mg 3 times daily. Metoprolol was then added to the therapeutic regimen of both groups for a further 12 weeks. Both nifedipine and metoprolol used as mono-therapy caused statistically significant reductions of arterial pressure. The addition of metoprolol to nifedipine tended to reduce blood pressure further, but blood pressures were not significantly lower than during nifedipine mono-therapy. Side-effects were few and only two patients had to be withdrawn during active therapy, one for headaches during nifedipine therapy, and another for asthma during metoprolol treatment. Combined therapy with a beta-adrenoceptor blocking agent, such as metoprolol, and a calcium antagonist with vasodilating properties, such as nifedipine, offers a theoretically interesting approach in the treatment of hypertension, even though the practical outcome in the present study probably suffered from an inadequate dose of nifedipine during the period of combined therapy.     

Effect of nebivolol on renal nitric oxide availability and tubular function in patients with essential hypertension

Aims

Nebivolol is a selective β₁-receptor antagonist with vasodilating properties. In patients with essential hypertension, we tested the hypothesis that nebivolol increases systemic and renal nitric oxide (NO) availability using L-N^G-monomethyl arginine (L-NMMA) as an inhibitor of NO production.

Methods

In a randomized, placebo-controlled, crossover study, patients with essential hypertension were treated with nebivolol for five days, along with a standardized diet and fluid intake. We examined the acute effects of systemic NO synthase inhibition with L-NMMA on brachial blood pressure (bBP), pulse wave velocity (PWV) and central blood pressure (cBP) estimated by applanation tonometry, glomerular filtration rate (GFR), fractional excretion of sodium (FE_Na), urinary excretion of both aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaC_γ), and plasma concentrations of nitrate/nitrite (p-NO_x) and vasoactive hormones after five days'' treatment with placebo and nebivolol.

Results

Nebivolol significantly reduced PWV, bBP, cBP and plasma renin, angiotensin II and aldosterone concentrations. The renal parameters, p-NO_x and plasma arginine vasopressin concentration were not changed by nebivolol. There was no difference between nebivolol and placebo in the response to L-NMMA, with LMMA inducing a similar increase in PWV, bBP and cBP and a similar decrease in GFR, uAQP2 and u-ENaC_γ and FE_Na [mean change −0.62% (95% confidence interval {CI} −0.40 to −0.84) during placebo vs. −0.57% (95% CI −0.46 to −0.68; P = 0.564) during nebivolol treatment]. Vasoactive hormones were changed to a similar extend by L-NMMA during administration of nebivolol and placebo.

Conclusions

Nebivolol did not change p-NO_x, and inhibition of NO synthesis induced the same response in blood pressure, GFR, renal tubular function and vasoactive hormones during nebivolol and placebo. Thus, the data did not support the hypothesis that nebivolol changes vascular and renal NO availability in patients with essential hypertension.     

Double-blind comparison of metoprolol,alprenolol, and oxprenolol in hypertension

Summary A double-blind comparison of the -blockers metoprolol, alprenolol and oxprenolol was carried out to evaluate their antihypertensive effect and tolerability. 105 patients with previously untreated hypertension entered the trial and 71 completed it. Side-effects were infrequent and were never the reason for drop-out. All three drugs caused a statistically significant reduction in blood-pressure at the lower of the two doses used during a dose-finding period. At the higher dose employed in this period, metoprolol caused a significantly greater reduction in diastolic blood-pressure than did alprenolol or oxprenolol. All three drugs caused a significant reduction in heart rate. During the follow-up period, the -blockers were supplemented if necessary with hydrochlorothiazide. This was required less frequently in the metoprolol group than in the other two groups.     

A state of art review on vardenafil in men with erectile dysfunction and associated underlying diseases

Introduction: Erectile dysfunction (ED) is a common male sexual disorder among men. Many governing bodies advocate the use of oral PDE5 inhibitors as a first-line therapy for ED. The clinical efficacy of these PDE5 inhibitors has been demonstrated in a number of placebo-controlled trials and reported by many systematic reviews on the effectiveness of PDE5 inhibitors in restoring the erectile function and improved frequency of successful sexual intercourse attempts across different spectra of underlying diseases.

Areas covered: This review article examines the drug profile of vardenafil and its role in restoring erectile function; highlights a number of clinical trials on vardenafil in men with underlying cardiovascular and metabolic conditions as well as in post-radical prostatectomy cases; and addresses the efficacy of vardenafil in comparison with other PDE5 inhibitors.

Expert opinion: Given the multi-factorial nature of ED, a holistic approach should be taken when dealing with ED patients. There is a need for long-term surveillance and management of underlying medical conditions, and despite the strict adherence to all the necessary steps to maximize its efficacy, PDE5 inhibitors could still fail due to the potential drug intolerance, progression of underlying disease or development of medical conditions.     

男性高血压患者血尿酸与勃起功能障碍及血管内皮损伤的关系#br#

摘要：目的　探讨男性高血压患者血清尿酸（UA）水平变化及其与勃起功能障碍（ED）和血管内皮损伤指标一氧化氮（NO）、内皮型一氧化氮合酶（eNOS）和内皮微粒（EMP）的关系。方法　选择新诊断男性高血压患者为研究对象,采用ED国际指数问卷表-5（IIEF-5）评估ED及其严重程度,100例伴ED患者（轻度31例、中度34例、重度35例）为ED组,100例年龄配对无ED的患者为对照组,尿酸酶法测定血清UA,酶联免疫法测定NO、eNOS,流式细胞技术测定血浆EMP水平。结果　重度ED组UA和EMP高于其他各组;而NO和eNOS低于其他各组,中度ED组UA和EMP高于轻度组及对照组;而NO和eNOS低于轻度组及对照组,轻度组UA和EMP高于对照组;而NO和eNOS低于对照组（P＜0.05）。相关分析表明高血压患者UA与NO、eNOS呈负相关,与EMP呈正相关（r分别为-0.589、-0.693和0.717,均P＜0.01）。多元逐步回归分析结果显示高血压患者UA、低密度脂蛋白胆固醇（LDL-C）、收缩压、糖尿病为EMP的影响因素,多元Logistic回归分析显示UA、舒张压、BMI及LDL-C为高血压患者ED的独立影响因素（P＜0.01）,血清UA预测高血压伴ED的ROC曲线下面积为0.785（95%CI：0.717～0.852,P＜0.01）。以血清UA 384.5 µmol/L作为预测ED最佳阈值时,敏感度90%,特异度69%,阳性预测值74.8%,阴性预测值87.3%。结论　高血压合并ED患者血清UA水平增高,高尿酸血症可能通过损伤血管内皮功能促使高血压患者ED发生与发展。     

Pharmacokinetic-pharmacodynamic (PK-PD) modeling of cardiovascular effects of metoprolol in spontaneously hypertensive rats: a microdialysis study

The present work addressed possible alterations in the pharmacokinetics and the in vivo pharmacodynamic of metoprolol (MET) in spontaneously hypertensive (SH) rats and Wistar Kyoto (WKY) animals by means of the microdialysis technique. The correlation between MET unbound plasma concentrations and its pharmacological effects, such as heart rate and blood pressure change, was also examined in SH and WKY rats by the application of a PK-PD model. MET dialysate concentrations and its chronotropic and blood pressure effect were determined during 3 h after the administration of 3 and 10 mg.kg⁻¹ of the drug. A PK-PD model with a separate effect compartment was used to analyse the data. A good correlation between plasma MET concentrations and its hypotensive and chronotropic effect was found in all experimental groups. Although a greater maximal effect (E_max) for the antihypertensive effect of MET was observed in SH rats (WKY: E_max: −17±1 mmHg; SH: E_max: −28±4 mmHg; P<0.05 versus WKY rats), no differences were found in the concentration yielding half-maximal response (IC₅₀) comparing SH (IC₅₀: 583±146 ng.ml⁻¹) and WKY animals (IC₅₀: 639±187 ng.ml⁻¹). The bradycardic effect of MET was greater in SH rats (E_max: −29±1%, P<0.05 versus WKY rats) than in WK animals (E_max: −22±2%), but no differences were observed in the IC₅₀ comparing both experimental groups (WKY: IC₅₀: 187±53 ng.ml⁻¹; SH: IC₅₀: 216±62 ng.ml⁻¹). Pharmacokinetic analysis shows that the volume of distribution of MET was greater in SH rats (Vd: 3.4±0.5 l, P<0.05 versus WKY rats) with regard to Wistar Kyoto (WKY) animals (Vd: 1.9±0.2 l). The results suggest that the pharmacokinetic behaviour of metoprolol are modified in SH rats, resulting in an increased volume of distribution. A greater maximal efficacy to the hypotensive effect of metoprolol was observed in SH rats, suggesting participation of β-adrenoceptors in the maintenance of the hypertension. Also, a greater chronotropic response to metoprolol was found in the hypertensive group compared with WKY animals, suggesting that, at least in part, the greater cardiac effect of metoprolol explained the enhanced hypotensive response of the beta blocker in the SH animals.     

比法尔(前列腺素E1)乳膏治疗男性勃起功能障碍及其机制

前列腺素E1(PGE1)具有扩张血管作用，其乳膏制剂(比法尔乳膏)可引起阴茎海绵体平滑肌及动脉舒张，调节人类海绵体内的去甲肾上腺素释放，可用于治疗男性勃起功能障碍。经多中心，临床试验证实，比法尔乳膏作为局部用药，疗效迅速、安全、无全身毒副作用，为非侵入性治疗男性勃起功能障碍的良药。     

Haemodynamic effects and pharmacokinetics of felodipine at rest and during exercise in hypertensive patients treated with metoprolol or atenolol

Summary A study has been performed in thirteen patients with essential hypertension, WHO Class I–II, and a diastolic blood pressure 95 mm Hg, on beta-blocker (metoprolol or atenolol) monotherapy, who were also given felodipine 10 mg b.d. for 28 days. The acute and steady state blood pressure response at rest and during exercise, and the pharmacokinetics of felodipine and metoprolol, were examined.Felodipine in combination with the beta-blocker reduced the systolic and diastolic blood pressures acutely and at steady-state. The duration of the effect was longer at steady-state. There was a significant correlation between the plasma concentration of felodipine and the change in blood pressure. The increase in systolic blood pressure during exercise was of the same magnitude before and after felodipine administration. No change in resting supine heart rate was found after the administration of felodipine.There were no significant differences in the pharmacokinetics of felodipine during long-term treatment, except for the trough plasma concentration, which was increased at steady-state, even though cumulation of felodipine and its metabolite did not occur. There was a significant decrease in the maximal plasma concentration and AUC of metoprolol after 28 days of treatment with felodipine, but its elimination half-life was not changed.The adverse reactions reported during this study were those generally seen after dihydropyridines and, except for two patients who were withdrawn after the first study day, the effects were well tolerated.     

培哚普利与美托洛尔对高血压病左室肥厚及糖、胰岛素代谢的影响

目的 :观察培哚普利与美托洛尔治疗原发性高血压的降血压疗效及其对左心室肥厚 (LVH)、糖与胰岛素代谢的影响。方法 :74例原发性高血压且无糖尿病病人 ,随机分为 2组 ,培哚普利组用培哚普利 4～ 8mg ,po ,qd ,美托洛尔组用美托洛尔12 .5～ 5 0mg ,po ,bid ,治疗 2 4wk。比较治疗前后血压、左心室重量指数 (LVWI)、空腹血糖、空腹胰岛素的变化。结果 :两者均能显著降低血压 ,培哚普利治疗 2 4wk后LVWI明显减轻 ,空腹胰岛素较治疗前下降 ,空腹血糖略有降低。美托洛尔对LVWI及空腹血糖、空腹胰岛素无影响。结论 :培哚普利和美托洛尔均能明显降低血压 ,培哚普利降压的同时可能减轻LVH、改善胰岛素代谢     

Response of blood pressure and plasma norepinephrine to propranolol,metoprolol and clonidine during isometric and dynamic excercise in hypertensive patients

Summary The effects of metropolol (beta₁-selective), propranolol (nonselective) and clonidine (central alpha-stimulant) on plasma norepinephrine, blood pressure and heart rate were assessed at rest, during isometric work and dynamic exercise in 15 patients with moderate hypertension. Metroprolol resulted in a lower diastolic blood pressure during isometric and dynamic exercise than propranolol, which was paralleled by a lower plasma norepinephrine level during dynamic work; both beta-adrenergic blocking compounds resulted in a lower heart rate in all test situations than that obtained with clonidine; clonidine produced similar control of diastolic blood pressure to that obtained with the beta-adrenergic blocking agents, but did not clearly attenuate the systolic blood pressure response to dynamic exercise. Plasma norepinephrine concentrations tended to be lowest following clonidine, especially during dynamic work. The findings support the hypothesis that the central action of clonidine inhibits peripheral release of norepinephrine, but is insufficient to attenuate cardiac stimulation by physical exercise. The fact that propranolol caused higher plasma norepinephrine concentrations than metoprolol during exercise may explain the difference in the blood pressure responses during exercise.     

An oral yohimbine/L-arginine combination (NMI 861) for the treatment of male erectile dysfunction: a pharmacokinetic, pharmacodynamic and interaction study with intravenous nitroglycerine in healthy male subjects

AIMS: Interaction of phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction with organic nitrates could lead to severe hypotension. NMI 861 is a combination of 7.7 mg yohimbine tartrate and 6 g l-arginine glutamate. A similar oral combination, which contains the same amount of yohimbine and L-arginine, has been shown to improve erectile function in previous studies. METHODS: In two placebo-controlled, randomized, double-blind, two-way crossover design studies we aimed to assess first the pharmacokinetics and pharmacodynamics of a single oral dose of NMI 861 administered in 16 healthy male subjects, and then the pharmacodynamics of orally administered NMI 861 in combination with intravenous nitroglycerine (GTN) in 12 healthy male subjects. Systolic (SBP) and diastolic (DBP) blood pressures, pulse rate and adverse events were measured in each study. RESULTS: NMI 861 was well tolerated by all subjects with no significant adverse reactions reported. For L-arginine, mean C(max) +/- SEM (range) was 42 +/- 2.2 (28-63) microg ml(-1) and t(max) (range) was 0.88 (0.50-1.5) h. AUC and t(1/2) were not calculated for L-arginine because of the presence of endogenous concentrations and the contribution from food sources. For yohimbine, mean C(max) was 42 +/- 11 (2.8-128) ng ml(-1); t(max) was 0.57 (0.25-1.0) h; mean AUC(0,8 h) was 65 +/- 24 (5.4-332), ng ml(-1) h and t(1/2) was 1.0 +/- 0.34 (0.40-6.0) h. There was a small but significant difference in the mean change from baseline for SBP from 0 to 6 h after NMI 861 treatment compared with placebo (0.8 +/- 1.4 vs-4.1 +/- 2.1 mmHg, respectively; 95% CI 0.0, 9.8 mmHg (P = 0.047)). There was no significant difference in SBP between treatments for the studied periods 6-12 h and 12-24 h. There was no significant difference in DBP or pulse between NMI 861 and placebo treatments for the three studied time periods. In the study designed to investigate the interaction of organic nitrate with NMI 861, subjects were infused intravenously with increasing doses of GTN (15 min each dose) at 2.5, 5, 10, 20 and 40 microg min(-1) starting 40 min after a single oral dose of either NMI 861 or placebo. There was no significant difference in the hypotensive response induced by GTN between the NMI 861 and placebo treatments. The mean maximum changes from baseline during GTN infusion for subjects administered with either NMI 861 or placebo were a decrease of 16.9 +/- 3.4 vs 13.6 +/- 2.4 mmHg (mean difference between treatments -3.3 mmHg, 95% CI -12.7, 6.0 mmHg (P = 0.460)) for SBP, a decrease of 14.7 +/- 2.0 vs 14.0 +/- 2.0 mmHg for DBP (mean difference -0.7 mmHg, 95% CI -8.2, 6.8 mmHg (P = 0.835)), and an increase of 11.8 +/- 1.9 vs 14.1 +/- 2.4 beats min(-1) for pulse, respectively (mean difference -2.3 beats min(-1), 95% CI -9.3, 4.5 beats min(-1) (P = 0.464)). CONCLUSIONS: Acute oral administration of NMI 861 was found to be well tolerated and bioavailable in healthy male subjects and no significant hypotensive interaction with intravenous GTN was detected at the doses investigated.