Summary of the practice guideline 'Hypertension' (third division) from the Dutch College of General Practitioners

The revised practice guideline on hypertension from the Dutch College of General Practitioners has been brought in agreement with the guideline on hypertension from the Dutch Institute for Health Care Improvement. The main changes with regard to the former edition are: The threshold values for the diagnosis 'hypertension' have been lowered to 140 mmHg and 90 mmHg for the systolic and diastolic blood pressures, respectively. Annual screening for hypertension in the elderly is no longer recommended. Henceforth, blood pressure measurement once every five years is considered sufficient, unless the blood pressure is known to be in a borderline area in which treatment is being considered. Often, the decision as to whether a patient should take antihypertensive drugs no longer depends on the presence of hypertension as such: to receive drug treatment, the patient should have at least a 20% risk of developing a cardiovascular disease in the next 10 years. To aid in estimating this risk for individual patients a risk table has been devised. Diuretics and beta-blockers are the drugs of first choice. If the blood pressure remains too high, angiotensin-converting-enzyme (ACE) inhibitors and calcium-channel blockers may be added.     

A prospective evaluation of persistence on antihypertensive treatment with different antihypertensive drugs in clinical practice

Persistence on treatment affects the efficacy of antihypertensive treatment. We prospectively investigated the persistence on therapy and the extent of blood pressure (BP) control in 347 hypertensive patients (age 59.4 +/- 6 years) randomly allocated to a first-line treatment with: angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers (CCBs), beta-blockers, angiotensin-II receptor blockers (ARBs), or diuretics and followed-up for 24-months. Persistence on treatment was higher in patients treated with ARBs (68.5%) and ACE inhibitors (64.5%) vs CCBs (51.6%; p < 0.05), beta-blockers (44.8%, p < 0.05), and diuretics (34.4%, p < 0.01). No ARB, ACE inhibitor, beta-blocker, or diuretic was associated with a higher persistence in therapy compared with the other molecules used in each therapeutic class. The rate of persistence was significantly higher in patients treated with lercanidipine vs others CCBs (59.3% vs 46.6%, p < 0.05). Systolic and diastolic BP was decreased more successfully in patients treated with ARBs (-11.2/-5.8 mmHg), ACE inhibitors (-10.5/-5.1 mmHg), and CCBs (-8.5/-4.6 mmHg) compared with beta-blockers (-4.0/-2.3 mmHg p < 0.05) and diuretics (-2.3/-2.1 mmHg, p < 0.05). No ARB, ACE inhibitor, beta-blocker, or diuretic was associated with a higher BP control compared with the other molecules used in each therapeutic class. A trend toward a better BP control was observed in response to lercanidipine vs other CCBs (p = 0.059). The present results confirm the importance of persistence on treatment for the management of hypertension in clinical practice.     

Risk factors to be considered at the beginning of antihypertensive therapy in diabetes mellitus

The treatment of hypertension in diabetic patients due to its high prevalence rate belongs to the everyday clinical practice of internists, diabetologists and general practitioners. The main points of the initiation on of antihypertensive treatment in diabetic patients are reviewed. In order to decrease the target organ damages the treatment of early recognized cardiovascular risk factors are of great importance. The target value of antihypertensive treatment in diabetic patients is < 130/80 mmHg (in case of proteinuria > 1 g daily: < 125/75 mmHg). The global cardiovascular risk is high or very high in diabetic patients both with grade I-III hypertension and with high normal blood pressure, therefore, treatment with antihypertensive drug (besides life style optimalisation) should be initiated promptly in these cases. In case of micro- or macroalbuminuria antihypertensive drug (mainly with characteristics of blocking the renin-angiotensin-system) should be given to each diabetic subject irrespective of actual blood pressure values. Success of antihypertensive treatment in diabetic patients could be achieved mainly with combination therapy only. It is reasonable to initiate antihypertensive therapy primarily with a low dose combination of two agents in diabetic patients with hypertension.     

Olmesartan medoxomil combined with hydrochlorothiazide for the treatment of hypertension

In most patients with hypertension, especially Stage 2 hypertension, adequate control of blood pressure (BP) is only achieved with combination drug therapy. When using combination therapy, antihypertensive agents with complementary mechanisms of action are recommended, for example, an angiotensin receptor blocker (ARB) in combination with hydrochlorothiazide (HCTZ), a beta-blocker + HCTZ, an ACE inhibitor + HCTZ, or a calcium channel blocker + an ACE inhibitor. One such combination is olmesartan medoxomil + HCTZ, which is available as fixed-dose, single-tablet combinations for once-daily administration. In clinical trials, olmesartan medoxomil/HCTZ reduced systolic BP (SBP) and diastolic BP (DBP) to a greater extent than either component as monotherapy. A clinical study in patients with Stage 1 or 2 hypertension showed that olmesartan medoxomil/HCTZ achieved a similar mean reduction in DBP, but a significantly greater mean reduction in SBP and higher rate of BP control (< 140/90 mmHg) than observed with losartan/HCTZ, at US/European-approved starting doses. In a non-inferiority trial, the antihypertensive efficacy of olmesartan medoxomil/HCTZ was comparable to that of atenolol/HCTZ. Furthermore, indirect comparisons have shown that olmesartan medoxomil/HCTZ compares favorably with other antihypertensive combination therapies, including other ARB/HCTZ combinations and amlodipine besylate/ benazepril. Olmesartan medoxomil/HCTZ is generally well tolerated. In conclusion, olmesartan medoxomil/HCTZ is an effective and well-tolerated combination antihypertensive therapy that results in significant BP reductions and BP control in many patients.     

Calcium channel blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors: effectiveness in combination with diuretics or beta-blockers for treating hypertension

This retrospective database analysis compared the effectiveness of dihydropyridine calcium channel blockers (DHPs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) added to diuretics or beta-blockers. Adults with hypertension treated with diuretic or beta-blocker monotherapy between 1998 and 2001 were identified from a large US electronic medical records database of primary care practices. Patients were required to have a baseline blood pressure (BP) > or =140/90 mmHg (> or =130/80 mmHg for diabetes mellitus) and recorded BP measurements within 6 months before and 1-12 months following index date. Patients were matched 1:1:1 by propensity score to correct for differences in baseline characteristics. 1875 patients met study criteria and 660 (220 in each cohort) were matched based on propensity scores. Matched cohorts had no significant differences in baseline characteristics. Mean changes in systolic/diastolic BP were -17.5/-8.8, -15.7/-6.3, and -13.0/-8.0 mmHg with DHPs, ACE inhibitors, and ARBs, respectively. Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High BP 6/7 goal attainment for each regimen was 47.3%, 40.0%, and 32.2%, respectively. DHPs, ACE inhibitors, and ARBs improved BP when added to patients' beta-blocker or diuretic therapy. The greatest benefits were observed with DHPs, followed by ACE inhibitors, then ARBs.     

Summary of the practice guideline 'Diabetes mellitus type 2' (second revision) from the Dutch College of General Practitioners

The practice guideline 'Diabetes mellitus type 2' (second revision) addresses the diagnosis, treatment and management of adults with diabetes mellitus type 2 in general practice. The aim of management is the prevention and treatment of diabetes-related symptoms and complications such as cardiovascular disease, nephro-, retino- and neuropathy. The general practitioner gives the patient education and lifestyle advice and repeats this regularly. In addition, the general practitioner and the patient strive to achieve good glycaemic control. The agent of first choice in the medicinal treatment of all type 2 diabetic patients is metformin. This is continued even after the addition of a sulphonylurea derivative or insulin. This represents a change compared to the previous version of the practice guideline. The indications for thiazolidinediones are limited. To reduce the cardiovascular risk, it is advised to aim at a systolic blood pressure below 140 mmHg. It is also recommended that each patient be prescribed a statin, unless the patient belongs to a subgroup in which the indication for cholesterol lowering therapy is weak or the patient refuses it. Compared to the former guideline, more emphasis is placed on the prevention of nephropathy. The general practitioner is advised to calculate the creatinine clearance yearly and to test for relevant albuminuria in each patient with a life expectancy of 10 years or more. If microalbuminuria is present, the patient is prescribed an angiotensin converting enzyme (ACE) inhibitor, even if the blood pressure is not elevated. The detection of patients with a high risk of diabetic ulcer is also given more emphasis.     

Drug therapy for hypertension in the elderly

Essential hypertension is a major health care problem in the elderly and requires effective treatment to reduce morbidity and mortality. The traditional stepped-care approach to therapy consisted of diuretics; sympatholytic agents, or beta-blockers for all age groups. Indeed, initial therapy with these agents is effective in 50 to 60 percent of elderly patients but may produce adverse effects. A high incidence of adverse responses, including sexual dysfunction and central nervous system impairment, has been reported with diuretic or beta-blocker therapy, and a reduction in several measures of quality of life has been noted during therapy with methyldopa or propranolol. Administration of an angiotensin-converting enzyme (ACE) inhibitor is as effective as the traditional stepped-care approach without producing the ill effects associated with diuretics, sympatholytics, or beta-blockers. The combination of an ACE inhibitor with a diuretic produces additive antihypertensive effects while minimizing diuretic-induced metabolic alterations. Orthostatic hypotension with the first dose can be minimized by making sure that patients are not hypovolemic from previous diuretic therapy. Nevertheless, in controlled trials, the combination of ACE inhibitor and diuretic has been effective in up to 85 percent of patients. In addition, the use of ACE inhibitors may be beneficial in the hypertensive patient with concomitant congestive heart failure. Most important, the patient's quality of life is maintained during therapy with an ACE inhibitor alone or in combination with a diuretic. Thus, an ACE inhibitor plus a diuretic is a valuable alternative to traditional antihypertensive therapy in elderly patients.     

Applying quality of life data in practice. Considerations for antihypertensive therapy

Quality of life issues have become increasingly important in tailoring antihypertensive therapy to individual patients. The application of quality of life data to the practice setting is frequently difficult, however. The effective use of this information requires an understanding of its definition and measurement, as well as of study methods. Quality of life findings may be specific to particular disease states, patient populations, and pharmacologic agents. The addition of hydrochlorothiazide to concurrent methyldopa, propranolol, or captopril therapy has been reported to reduce patients' overall sense of well-being. beta-Adrenergic blockers may exert either positive or negative effects on quality of life. Angiotensin-converting enzyme (ACE) inhibitors may have positive effects on quality of life; however, the cost of therapy is an important consideration. Information on calcium antagonists is limited. The findings of the Treatment of Mild Hypertension Study (TOMHS) may eventually provide comparative quality of life data on the four first-line antihypertensive therapies.     

High blood pressure-lowering and vasoprotective effects of milk products in experimental hypertension

Milk casein-derived angiotensin-converting enzyme (ACE)-inhibitory tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) have been shown to have antihypertensive effects in human subjects and to attenuate the development of hypertension in experimental models. The aim of the present study was to investigate the effect of a fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro and plant sterols on already established hypertension, endothelial dysfunction and aortic gene expression. Male spontaneously hypertensive rats (SHR) with baseline systolic blood pressure (SBP) of 195 mmHg were given either active milk (tripeptides and plant sterols), milk or water ad libitum for 6 weeks. SBP was measured weekly by the tail-cuff method. The endothelial function of mesenteric arteries was investigated at the end of the study. Aortas were collected for DNA microarray study (Affymetrix Rat Gene 1.0 ST Array). The main finding was that active milk decreased SBP by 16 mmHg compared with water (178 (SEM 3) v. 195 (SEM 3) mmHg; P < 0.001). Milk also had an antihypertensive effect. Active milk improved mesenteric artery endothelial dysfunction by NO-dependent and endothelium-derived hyperpolarising factor-dependent mechanisms. Treatment with active milk caused mild changes in aortic gene expression; twenty-seven genes were up-regulated and eighty-two down-regulated. Using the criteria for fold change (fc) < 0.833 or > 1.2 and P < 0.05, the most affected (down-regulated) signalling pathways were hedgehog, chemokine and leucocyte transendothelial migration pathways. ACE expression was also slightly decreased (fc 0.86; P = 0.047). In conclusion, long-term treatment with fermented milk enriched with tripeptides and plant sterols decreases SBP, improves endothelial dysfunction and affects signalling pathways related to inflammatory responses in SHR.     

Hypertension in the Negro patient

Essential hypertension appears to be more prevalent among blacks than among whites and has an earlier onset in blacks. Many data in this field come from studies in the African-American population. Hypertension-related complications, e.g. ischaemic heart disease, (end stage) renal failure and cerebrovascular disease, are encountered more often among blacks and frequently run a more severe course. Factors that might explain the racial difference in prevalence of hypertension and hypertensive complications include both genetic and environmental variables. Hypertension in blacks is characterized by salt sensitivity, a tendency towards expanded plasma volume and low plasma renin levels. Socioeconomic factors, the higher prevalence of obesity and insulin resistance may contribute to the high prevalence of hypertension in blacks. Aggressive antihypertensive therapy appears mandatory in the black hypertensive, possibly with lower goal blood pressures than the 140/90 mmHg generally recommended. Diuretic monotherapy proves to be the first-line therapy, calcium channel blockers are an attractive alternative. Black patients are frequently less responsive to monotherapy with angiotensin-converting enzyme (ACE) inhibitors and beta-blocking agents. This black/white difference in therapeutic response can, however, be eliminated by addition of a diuretic.     

The practice guideline 'Hypertension' (third revision) from the Dutch College of General Practitioners; a response from the perspective of internal medicine

The revised practice guideline on hypertension from the Dutch College of General Practitioners is a useful document for the management of hypertension. The decision to limit antihypertensive treatment to patients with at least a 20% risk of developing cardiovascular disease within 10 years may, however, be criticised. Prolonged untreated mild hypertension may lead to macro- and microvascular myocardial sclerosis and disturbed systolic and diastolic function of the left ventricle. A 10% risk is preferred. On the other hand, case-finding and treatment of patients with hypertension will increasingly be a major time-consuming activity in general practice. This calls for a change in organisation: well-trained vascular assistants should be employed to fulfill most of this task.     

The applicability of home blood pressure measurement in clinical practice: a review of literature

Purpose

To review the literature on home blood pressure measurement (HBPM), to examine its validity and applicability for clinical practice and to provide recommendations regarding HBPM assessment.

Findings

HBPM can eliminate the white coat effect and offers the possibility to obtain multiple measurements under standardized conditions, which increases knowledge of overall blood pressure value. Although it is not entirely capable of replacing ambulatory blood pressure measurement (ABPM), HBPM correlates better with target organ damage and cardiovascular mortality than office blood pressure measurement (OBPM), it enables prediction of sustained hypertension in patients with borderline hypertension, and proves to be an appropriate tool for assessing drug efficacy. Additional advantages of HBPM are that it may increase drug compliance and patient’s awareness of hypertension. Overall, OBPM yield higher blood pressure values than HBPM. Differences between OBPM and HBPM tend to increase with age and are generally higher in patients without antihypertensive treatment than in patients with antihypertensive treatment.

Recommendations

Measurements should be performed according to accepted guidelines and recordings should be performed with a memory equipped automatic validated device. From the data reviewed here, we recommend that HBPM be assessed monthly by taking two measurements in the morning within 1 hour after awakening and two in the evening for three consecutive days, the data from the first day should be dismissed. A subject should be labeled hypertensive if his/her HBPM value is equal to or greater than 137 mmHg systolic and/or 84 mmHg diastolic.     

Relatively poor regulation of blood pressure in patients with type-2 diabetes mellitus in the primary care setting and specialists' practice in the Netherlands

OBJECTIVE: To investigate the degree to which the goals for adequate blood-pressure control in patients with type-2 diabetes mellitus (DM) are met in Dutch specialists' practice and in the primary-care setting. DESIGN: Cross sectional. METHOD: Data were collected from all consecutive patients with DM type 2 visiting the outpatient clinic of two physicians specialised in diabetes care, in Zwolle, the Netherlands, in the period 1 November 1999-30 April 2000. The target value for blood pressure was < or = 150/85 mmHg. In addition, baseline data were collected on patients in the primary-care setting who participated in a transmural project in Zwolle in the period 1 February 1997-31 January 1998. In 1998, the target blood pressure in the primary-care setting was < or = 160/90 mmHg. Patients who met the goals for adequate blood-pressure control were compared with patients who did not. RESULTS: A total of 502 patients from specialists' practice and 1084 patients from the primary-care setting were included. The prevalence of hypertension in specialists' practice was 89% (n = 377); of these patients, 140 (37%) had a good regulation of their blood pressure. The patients who had an adequate blood-pressure control and those who did not were comparable. Both groups were prescribed an average of 2.2 kinds of antihypertensive agent per patient. The prevalence of hypertension in the primary care was 69% (n = 733). The goal for adequate blood-pressure control, i.e. a blood pressure of < or = 160/90 mmHg, was achieved in 44% (n = 324). In the primary-care setting, an average of 1.1 kinds of antihypertensive agent was prescribed, 1.6 in patients who achieved the target value and 0.8 in those who did not (p < 0.05). CONCLUSION: Regulation of blood pressure in patients with type 2 DM and hypertension was far from optimal: 37% of patients in specialists' practice and 44% of those in the primary-care setting achieved the target values.     

Use of antihypertensive drug therapy in older persons in an academic nursing home

OBJECTIVES: To determine the prevalence of hypertension and the appropriate treatment of hypertension in older persons in an academic nursing home. DESIGN: The charts of all persons aged > or = 59 years currently residing in a nursing home affiliated with Westchester Medical Center/New York Medical College were analyzed by two geriatrics fellows according to a protocol designed by one of the authors (W.S.A.). SETTING: An academic nursing home affiliated with Westchester Medical Center/New York Medical College. PARTICIPANTS: The study population included 96 men and 159 women, mean age 77 +/- 9 years (range, 59-100 years). RESULTS: Hypertension was present in 129 of 255 persons (51%). Clinical cardiovascular disease or target organ damage or diabetes mellitus was present in 121 of 129 persons (94%) with hypertension. Hypertension was poorly controlled in 21 of 129 persons (16%). Of 129 persons with hypertension, 70 (54%) were treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers, 61 persons (47%) with beta blockers, 43 persons (33%) with diuretics, 36 persons (28%) with calcium channel blockers, 5 persons (4%) with alpha blockers, and 5 persons (4%) with other antihypertensive drugs. Of 54 persons with hypertension and diabetes mellitus, 37 persons (69%) were treated with ACE inhibitors or angiotensin II type 1 receptor blockers. Of 58 persons with hypertension and coronary artery disease, 33 persons (57%) were treated with ACE inhibitors or angiotensin II type 1 receptor blockers, 31 persons (53%) with beta blockers, 20 persons (34%) with diuretics, 18 persons (31%) with calcium channel blockers, 2 persons (4%) with alpha blockers, and 4 persons (7%) with other antihypertensive drugs. Of 31 persons with hypertension and heart failure, only 5 persons (16%) had measurement of left ventricular ejection fraction. Of 31 persons with hypertension and heart failure, 30 persons (97%) were treated with diuretics, 21 persons (68%) with ACE inhibitors or angiotensin II type 1 receptor blockers, 18 persons (58%) with beta blockers, and 8 persons (26%) with calcium channel blockers. CONCLUSIONS: Of older persons with hypertension in an academic nursing home, 16% had poor control of their hypertension. There was overuse of calcium channel blockers and alpha blockers and underuse of diuretics, beta blockers, and ACE inhibitors in treating hypertension. Physician education needs to be intensified to provide better medical care of older persons with hypertension through the use of optimal doses of drugs found to be effective and safe by evidence-based studies.     

The practice guideline 'Diabetes mellitus type 2' (second revision) from the Dutch College of General Practitioners; a response from the perspective of internal medicine

The revised guideline 'Diabetes mellitus type 2' contains several improvements. The HbA1C target level has been lowered to 7% or less. The universal first step in oral therapy has become metformin. The target level for the treatment of hypertension is now a systolic pressure below 140 mmHg. Statins should be prescribed to almost every patient. Finally, ACE-inhibitors are now suggested for all patients with microalbuminuria and hypertension. Some choices made in the present guideline are not evidence-based, e.g. the advice to prescribe pioglitazone to patients with both a body mass index above 27 kg/m2 and cardiovascular disease, but without heart failure. Still, in general, the updated guideline is an important document which has been greatly improved in comparison to the former one.     

Trends in hypertension prevalence and management in Southwestern France, 1985-1996

The changes occurring in Southwestern France between 1985 and 1996 in hypertension prevalence, awareness and control were assessed in 622 men and 626 women for 1985 and in 614 men and 569 women for 1996. In women, prevalence of hypertension (defined as systolic blood pressure 160 mmHg and/or diastolic blood pressure 95 mmHg and/or presence of antihypertensive treatment) was 19% and 19% (NS), awareness was 67% and 87% (P < 0.001), treatment was 85% and 87% (NS) and control was 44% and 68% (P < 0.01) in the first and the second surveys, respectively. In men, prevalence of hypertension was 28% and 21% (P < 0.01), awareness was 47% and 71% (P < 0.001), treatment was 81% and 80% (NS) and control was 41% and 58% (NS). After stratifying on survey, women received significantly more beta-blockers and significantly less calcium channel blockers and ACE inhibitors than men, but those differences became nonsignificant after adjusting for other cardiovascular risk factors. We conclude that in Southwestern France, screening and management of hypertension have improved significantly, but more than one-third of treated hypertensive subjects still lacks adequate control.     

高血压患者治疗后血压昼夜节律及影响因素的调查

目的了解高血压病患者经治疗血压达标后血压昼夜节律及影响因素.方法采用横断面调查的方法,采用进入法进行非条件logistic回归分析.结果共纳人208例患者,呈勺型曲线者79例(占38%),非勺型曲线者129例(占62%).logistic回归分析显示,年龄在70岁以上及60～69之间者24 h动态血压曲线呈非勺型的比例分别是60岁以下者的3.3倍(P=0.009)和2.3倍(P=0.031);有早发心血管疾病家族史的患者,其动态血压曲线形态呈非勺型的比例为无相应家族史患者的3.7倍(P=0.029);超重(BMI＜28)与肥胖(BMI≥28)者24 h动态血压曲线呈非勺型的比例分别是正常体重(BMI＜24)者的3.0倍(P=0.003)和4.8倍(P=0.009);与单独应用长效钙离子拮抗剂(CCBs)治疗相比,单用血管紧张素转换酶抑制剂(ACEIs)或血管紧张素Ⅱ受体阻滞剂(ARBs)治疗者动态血压曲线呈非勺型的机会较少(OR=0.139,P=0.010),采用包含ACEIs或ARBs(但不包括利尿剂)的联合用药方案的患者有较少非勺型曲线的趋势,但二组之间差异无显著性(OR=0.453,P=0.118);采用包括利尿剂(但无ACEIs或ARBs)的联合用药方案以及同时包含利尿剂与ACEIs或ARBs的联合用药方案的患者均有较少非勺型曲线的机会(OR值分别为0.378和0.273,P值分别为0.030和0.011).结论高血压患者经治疗血压达标后,有近三分之二的患者呈异常的血压昼夜节律.年龄、早发心血管疾病的家族史、超重或肥胖、降压药物治疗方案等4个因素与24 h血压曲线形态有关.与单用长效CCBs比较,利尿剂、ACEIs或ARBs可能有利于保持正常的血压昼夜节律.     

Sexual function in hypertensive patients receiving treatment

In many forms of erectile dysfunction (ED), cardiovascular risk factors, in particular arterial hypertension, seem to be extremely common. While causes for ED are related to a broad spectrum of diseases, a generalized vascular process seems to be the underlying mechanism in many patients, which in a large portion of clinical cases involves endothelial dysfunction, ie, inadequate vasodilation in response to endothelium-dependent stimuli, both in the systemic vasculature and the penile arteries. Due to this close association of cardiovascular disease and ED, patients with ED should be evaluated as to whether they may suffer from cardiovascular risk factors including hypertension, cardiovascular disease or silent myocardial ischemia. On the other hand, cardiovascular patients, seeking treatment of ED, must be evaluated in order to decide whether treatment of ED or sexual activity can be recommended without significantly increased cardiac risk. The guideline from the first and second Princeton Consensus Conference may be applied in this context. While consequent treatment of cardiovascular risk factors should be accomplished in these patients, many antihypertensive drugs may worsen sexual function as a drug specific side-effect. Importantly, effective treatment for arterial hypertension should not be discontinued as hypertension itself may contribute to altered sexual functioning; to the contrary, alternative antihypertensive regimes should be administered with individually tailored drug regimes with minimal side-effects on sexual function. When phosphodiesterase-5 inhibitors, such as sildenafil, tadalafil and vardenafil, are prescribed to hypertensive patients on antihypertensive drugs, these combinations of antihypertensive drugs and phosphodiesterase 5 are usually well tolerated, provided there is a baseline blood pressure of at least 90/60 mmHg. However, there are two exceptions: nitric oxide donors and alpha-adrenoceptor blockers. Any drug serving as a nitric oxide donor (nitrates) is absolutely contraindicated in combination with phosphodiesterase 5 inhibitors, due to significant, potentially life threatening hypotension. Also, a-adrenoceptor blockers, such as doxazosin, terazosin and tamsulosin, should only be combined with phosphodiesterase 5 inhibitors with special caution and close monitoring of blood pressure.     

In vitro intestinal transport and antihypertensive activity of ACE inhibitory pea and whey digests

Angiotensin I converting enzyme (ACE) inhibitory peptides cause an antihypertensive effect if they reach the systemic circulation. This was investigated for the high ACE inhibitory activity present in peas and whey in vitro gastrointestinal digests. The samples retained high ACE inhibitory activity when incubated in Caco-2 homogenates or rat intestinal acetone powder, both sources of small intestine peptidases. Only little ACE inhibitory activity was transported through Caco-2 cell monolayers in 1?h. As the Caco-2 model is tighter than intestinal mammalian tissue, sufficient absorption of these peptides might occur in vivo. After intravenous administration of 50?mg protein?kg^?1 BW in spontaneously hypertensive rats (SHR), pea digest exerted a transient, but strong antihypertensive effect of 44.4?mmHg. Whey digest exerted no effect at this dose. These results suggest that pea digest could be a promising source of ACE inhibitory peptides for use in the prevention and treatment of hypertension.