Compliance with antihypertensive treatment: implications for practice.
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Antihypertensive Agents↗
Biomedical subjects
H R Brunner
Publications and source records attributed to H R Brunner.
Heterogeneous vascular response to vasopressin: radial artery versus forearm blood flow.
BACKGROUND: Arginine vasopressin (AVP) administered intra-arterially to normal volunteers exerts a biphasic effect on forearm blood flow when the effect is extrapolated from plethysmographic measurements. OBJECTIVE: To assess whether the high-dose AVP-induced increase in forearm blood flow could be confirmed when calculating blood flow from continuous radial artery diameter and flow velocity recordings obtained by using a high-resolution echotracking device combined with a Doppler system. METHODS: Increasing doses (0.04-0.8 ng/kg per min) of AVP were infused into a brachial artery of seven normal male volunteers (aged 21-33 years). Forearm blood flow derived from venous occlusion plethysmography was assessed simultaneously with proximal radial artery blood flow calculated from luminal area and flow velocity measurements. RESULTS: Confirming previous reports, plethysmography showed an increase in global forearm blood flow by > 100% with AVP concentrations > or = 0.2 ng/kg per min. In contrast, direct measurements of lumen diameter and blood flow velocity in the radial artery revealed a marked dose-dependent vasoconstriction with a > 30% decline in blood flow at the highest AVP concentration. CONCLUSIONS: The discrepancy between the two measurements suggests that AVP has a dual effect on forearm haemodynamics. At high AVP concentration, the muscle blood flow increase predominates over the vasoconstriction in the skin circulation. Furthermore, this study strongly suggests a heterogeneity of the vascular response to vasomediators by showing that opposing responses exist not only between resistive and conduit vessels but also between conduit arteries of a common vascular bed.
Adult↗
Low-dose combinations versus monotherapies in the treatment of hypertension.
RATIONALE FOR DRUG COMBINATIONS: Essential hypertension is a heterogeneous disease. Different factors might interact, in an individual patient, to increase blood pressure. This explains why a drug that lowers blood pressure by a given mechanism may normalize blood pressure in some patients but not in others. combining two drugs with complementary mechanisms of action can increase the antihypertensive efficacy. DOSAGES USED IN DRUG COMBINATIONS: When administered in combination, lower doses of the separate components are generally necessary than when the drugs are prescribed as monotherapies, which may improve tolerability. Fixed-dose combination therapy is therefore an attractive approach to the treatment of hypertensive patients. It may be an appropriate choice, not only for second-line, but also for first-line therapy.
Antihypertensive Agents↗
[Measurement of blood pressure: best way to assess cardiovascular risk?].
Measurement of the blood pressure by the physician remains an essential step in the evaluation of cardiovascular risk. Ambulatory measurement and self-measurement of blood pressure are ways of counteracting the "white coat" effect which is the rise in blood pressure many patients experience in the presence of doctors. Thus, it is possible to define the cardiovascular risk of hypertension and identify the patients with the greatest chance of benefiting from antihypertensive therapy. However, it must be realised that normotensive subjects during their everyday activities and becoming hypertensive in the doctor's surgery, may become hypertensive with time, irrespective of the means used to measure blood pressure. These patients should be followed up regularly even if the decision to treat has been postponed.
Antihypertensive Agents↗
Remodelling of conduit arteries in hypertension: special emphasis on the mechanical and metabolic consequences of vascular hypertrophy.
Vascular remodelling is well demonstrated in both human and experimental hypertension. Whether it develops in response to high blood pressure or as a marker of hypertension independently of any pressure level, it contributes in resistance arteries to maintaining an elevated blood pressure. Only recently, with the development of sensitive and reproducible methods, has remodelling of conduit arteries been assessed. A high resolution B-mode ultrasound technique can be used to measure arterial wall thickness and luminal dimension during the cardiac cycle. Changes in geometry and structure of conduit vessels have been observed in hypertensive patients or during experimental studies in animal models of hypertension. These changes may influence the buffering capacity of the conduit vessels, resulting in alteration of the dynamic component of the vascular impedance. Reduction of the systemic compliance may increase afterload and with time depress cardiac function. Ultrasonography apparatus is designed to measure local elastic properties and structural alterations and should be considered as such. Indeed, extrapolation of data acquired at a given arterial site to other parts of the vascular bed is hazardous. There exist other indirect methods based on pulse wave contour analysis and pulse wave velocity that can estimate global arterial compliance. Unfortunately, these methods have other limitations that restrict their use. Because conduit vessels represent one of the most important targets for pressure-induced lesions, namely atherosclerosis, they may be viewed as a surrogate endpoint in hypertension. Do we have evidence that vascular remodelling associated with hypertension predisposes to accelerated atherosclerosis? The purpose of this paper is to discuss the evidence that may support such a concept.
Arteries↗
[Angiotensin II antagonists: a distinct therapeutic class].
Angiotensin II antagonists are a promising new class of antihypertensive agents. Unlike angiotensin converting enzyme inhibitors, these new agents block the renin-angiotensin system by acting directly on the angiotensin II receptor. It is quite probable that these agents will become a first line therapeutic choice for hypertensive patients. Current clinical trials on primary prevention may confirm the indications for this new therapeutic class in a near feature.
Angiotensin II↗
Angiotensin II receptor inhibition. A new therapeutic principle.
Angiotensin II receptor antagonists represent a new class of drugs that provide a site-specific blockade of the effects of angiotensin II. Losartan potassium, the first compound of this drug class, has recently become available in the United States. The clinical experience with angiotensin II receptor antagonists has demonstrated that these drugs are safe and efficacious for the treatment of hypertension and, possibly, congestive heart failure. Unlike with angiotensin-converting enzyme inhibitors, the incidence of cough observed with angiotensin receptor antagonists is similar to that with placebo. Although several angiotensin receptors have been characterized, the effects of losartan and other angiotensin receptor antagonists under development are selective for the angiotensin II type 1 receptor. Unlike angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists do not inhibit bradykinin metabolism or enhance prostaglandin synthesis. The antihypertensive efficacy of the angiotensin receptor antagonists has been documented to be similar to that of angiotensin-converting enzyme inhibitors. If the findings of clinical studies corroborate the initial reports on efficacy and safety, it seems likely that the angiotensin receptor antagonists will be added to the list of drugs that have been deemed suitable for first-line therapy in the treatment of hypertension and congestive heart failure.
Angiotensin II↗
[Ambulatory blood pressure monitoring in the assessment of the hypertensive patient].
Non-invasive ambulatory blood pressure monitoring allows to record numerous blood pressures during everyday activities. The relationship between blood pressure and target organ damage is closer with ambulatory than conventional office blood pressures. Monitoring blood pressure outside the doctor's office appears more and more useful in diagnosing and treating hypertension. This approach makes it possible to recognize high-risk hypertensive patients, i.e. patients exhibiting abnormally increased blood pressures in the presence as well as in the absence of the doctor.
Antihypertensive Agents↗
[Diagnosis and treatment of arterial hypertension in the elderly].
The incidence of hypertension increases with age and becomes very high in the seventh decade. The increase of the blood pressure may be systolic, diastolic or both. Various controlled studies have shown that the treatment of hypertension in the elderly reduces the incidence of myocardial infarction and of stroke. It appears today that also patients with isolated systolic hypertension benefit from antihypertensive treatment. All classes of antihypertensive agents, including beta-blocking drugs, may be used in the elderly.
Aged↗
Changes in treatment during and after hospitalization in patients taking drugs for cardiovascular diseases.
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Cardiovascular Diseases↗
Renal effects of angiotensin II receptor blockade in normotensive subjects.
Several new non-peptide, orally active, angiotensin II receptor antagonists have recently been developed which enable to block the renin-angiotensin system at the AT1 receptor site. In contrast to angiotensin converting enzyme (ACE) inhibitors, these antagonists do not interfere with the metabolism of kinins. The effect of these agents on renal function may thus potentially differ from those of ACE inhibitors. Therefore, the renal pharmacology of various angiotensin II receptor antagonists has been examined in normotensive subjects. In normotensive subjects, losartan and irbesartan have been shown to have no effect on glomerular filtration rate and to induce either no change or a modest increase in renal blood flow. These results were confirmed thereafter in hypertensive patients where losartan produced a renal vasodilation with no change in glomerular filtration. In healthy subjects, both losartan and irbesartan induce an acute increase in urinary sodium excretion. The natriuretic response to losartan is proportionally more important during salt-depletion. In contrast to other angiotensin II receptor antagonists, losartan has a unique property to increase uric acid excretion. In this paper we show that this property is due to the potent inhibitory effect of the parent compound of losartan on the urate/anion transport in the human renal proximal tubule.
Angiotensin Receptor Antagonists↗
Isolated office hypertension: a prehypertensive state?
OBJECTIVE AND METHOD: Isolated office hypertension, defined as hypertensive blood pressure values in a medical setting but normal self-measured or ambulatory-recorded blood pressures, is frequently encountered in clinical practice. Yet, whether this condition represents a transient state in the development of a sustained ambulatory hypertension is still unknown as no long-term analysis of the evolution of ambulatory blood pressure has been carried out in patients with isolated office hypertension. To evaluate whether such patients should be considered as truly normotensive or hypertensive, we have studied the long-term changes in office and ambulatory blood pressures in 81 patients in whom isolated office hypertension was observed between 1982 and 1988. RESULTS: After a 5-6 year follow-up, 60 of the 81 patients had a mean 12 h daytime ambulatory blood pressure greater than 140/90 mmHg, suggesting an evolution towards ambulatory hypertension. The development of hypertension could not be predicted on the basis of the follow-up office blood pressures as these tended to decrease during the follow-up period. CONCLUSIONS: The results of this study suggest that patients with isolated office hypertension should not be considered as truly normotensive individuals. Hence, these patients require a careful medical follow-up. Office blood pressure readings alone, however, do not appear to provide a good indicator of the long-term outcome of isolated office hypertension.
Adolescent↗
Cardiovascular hypertrophy: role of angiotensin II and bradykinin.
Angiotensin II can raise blood pressure rapidly by inducing direct vasoconstriction and by activating the sympathetic nervous system via central and peripheral mechanisms. In addition, this peptide may act as a growth factor to cause vascular and cardiac hypertrophy (CVH). The structural changes caused by hypertension can therefore be amplified by angiotensin II. Blockade of angiotensin II generation with angiotensin-converting enzyme (ACE) inhibitors appears to be particularly effective in preventing the development of cardiovascular hypertrophy. This beneficial effect might be related to some extent to local accumulation of bradykinin. ACE is one of the enzymes physiologically involved in bradykinin degradation. Treatment of hypertensive rats with a selective bradykinin antagonist can attenuate the blood pressure-lowering effect of ACE inhibition and render less effective the prevention of intimal thickening after endothelial removal from the rat carotid artery. Bradykinin is a vasodilator that acts by increasing the release of endothelium-derived factors such as nitric oxide and prostacyclin, which may have antiproliferative activity. However, blockade of the renin-angiotensin system with an angiotensin II subtype 1-receptor antagonist is also effective in preventing cardiac hypertrophy and neointimal proliferation after endothelial injury. Therefore, the exact contribution of bradykinin to the beneficial effects of ACE inhibition on cardiovascular hypertrophy remains to be further explored.
Angiotensin II↗
Clinical and hormonal effects of the new angiotensin II receptor antagonist LRB081.
The renin-angiotensin system is a major contributor to the pathophysiology of cardiovascular diseases such as congestive heart failure and hypertension. Antagonizing angiotensin (Ang) II at the receptor site may produce fewer side effects than inhibition of the promiscuous converting enzyme. The present study was designed to assess in healthy human subjects the effect of LRB081, a new orally active AT1-receptor antagonist, on the pressor action of exogenous Ang II. At the same time, plasma hormones and drug levels were monitored. At 1-week intervals and in a double-blind randomized fashion, 8 male volunteers received three doses of LRB081 (10, 40, and 80 mg) and placebo. Blood pressure (BP) was measured at a finger by photoplethysmograph. The peak BP response to intravenous injection of a standard dose of Ang II was determined before and for < or = 24 h after administration of an oral dose of LRB081 or placebo. After drug administration, the blood BP response to Ang II was expressed in percent of the response before drug administration. At the same time, plasma renin activity (PRA), Ang II, aldosterone, catecholamine (radioassays), and drug levels (by high-performance liquid chromatography) were monitored. After LRB081 administration, a dose dependent inhibition of the BP response to Ang II was observed. Maximal inhibition of the systolic BP response was 54 +/- 3 (mean +/- SEM), 63 +/- 2, and 93 +/- 1% with 10, 40, and 80 mg LRB081, respectively. The time to peak was 3 h for 6 subjects and 4 and 6 h for 2 others. Preliminary plasma half-life (t1/2) was calculated at 2 h. With the highest dose, the inhibition remained significant for 24 h (31 +/- 5%, p < 0.05). Maximal BP-blocking effect and maximal plasma drug level coincided, suggesting that the unmetabolized LRB081 is responsible for the antagonistic effect. PRA and Ang II increased dose dependently after LRB081 intake. Aldosterone, epinephrine, and norepinephrine concentrations remained unchanged. No clinically significant adverse reaction was observed during the study. LRB081 is a well-tolerated, orally active, potent, and long-acting Ang II receptor antagonist. Unlike in the case of losartan, no active metabolite of LRB081 has been shown to be responsible for the main effects.
Adult↗
Do we need new antihypertensive drugs?
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Antihypertensive Agents↗
The renin-angiotensin system and the heart: beyond 2000.
Renin-angiotensin is both a circulatory and a local tissue system. However, in most circumstances, renin present in the heart and blood vessels is taken up from the plasma, and the kidney is the prime source of this renin. Tissues can then modulate and control the production of angiotensin II. In various organs, angiotensin II has local actions. In the heart, working through the AT1 receptor, it increases contractility and may cause cardiocyte hypertrophy. Indirectly, the heart is also very much affected by the vascular actions of angiotensin II. However, the net result on the heart is the product of an important interaction between a large number of factors. There is little doubt that an inappropriately high plasma (and tissue) level of renin, related to sodium balance, is associated with increased left ventricular hypertrophy and cardiovascular complications. The genetic approach will lead to an understanding of genomic risk factors in hypertension and may identify control systems--at present unknown--which will lead to a new approach to the prevention of cardiovascular death. It is, however, unlikely that such a factor will clearly predict an individual's prognosis, but it will, rather, identify groups at risk. Constellations of genomic interactions with multiple environment factors reduce this power. Modification of the response to angiotensin II using present treatment, or interrupting the response at more distal sites, may enable us to achieve the beneficial effects on cardiac hypertrophy without the detrimental effects.
Angiotensin II↗
Effects of neuropeptide Y on intrarenal hemodynamics, plasma renin activity and urinary sodium excretion in rats.
Neuropeptide Y (NPY) is a vasoconstrictor peptide possibly involved in the regulation of renal sodium handling and renin release. This investigation was undertaken to assess in conscious normotensive rats the acute effects of a non-pressor dose of NPY on renal plasma flow, glomerular filtration rate, sodium excretion and plasma renin activity. Experiments were also performed during concomitant beta-adrenoceptor stimulation with isoproterenol. NPY per se had no effect on the studied parameters. Renal plasma flow was increased by isoproterenol and was significantly higher when the beta-adrenoceptor stimulant was infused alone (13.4 +/- 2.1 ml/min, p < 0.05, mean +/- SEM) that when administered together with NPY (7.2 +/- 2.0 ml/min). This was also true for glomerular filtration rate (3.3 +/- 0.3 vs. 1.8 +/- 0.3 ml/min, p < 0.01) and plasma renin activity (6.3 +/- 1.7 vs. 2.1 +/- 0.4 ng Ang I/ml/h, p < 0.05). Our data however do not allow to deduce whether the inhibitory effect of NPY on isoproterenol-induced renin release is mediated by changes in intrarenal hemodynamics or a direct effect on juxtaglomerular cells.
Adrenergic beta-Agonists↗
Contributions of vascular tone and structure to elastic properties of a medium-sized artery.
Isobaric compliance and distensibility of the radial artery were recently reported to be normal or slightly increased in untreated hypertensive patients. However, these findings provide no information on the intrinsic mechanical properties of the wall material. To address this question, we determined intima-media wall thickness, wall-to-lumen ratio, and incremental elastic modulus in the radial artery of 25 untreated hypertensive patients with blood pressure of 150 +/- 14/103 +/- 6 mm Hg (mean +/- SD) and 25 matched control subjects with blood pressure of 118 +/- 9/79 +/- 6 mm Hg. High-resolution echotracking for assessment of internal diameter and intima-media wall thickness was combined with measurements of blood flow velocity by Doppler and blood pressure by photoplethysmography. In addition, isobaric compliance and distensibility and incremental elastic modulus were measured at peak diameter during reactive hyperemia after a 5-minute brachial occlusion. No significant difference was found between the two groups for isobaric compliance or distensibility at baseline or during hyperemia. However, incremental elastic modulus at 100 mg Hg tended to be lower in hypertensive patients than control subjects (1.9 +/- 1.1 versus 2.5 +/- 1.2 mm Hg x 10(4), P = .1) in resting conditions. Hypertensive patients and control subjects had similar internal diameters (2.47 +/- 0.32 versus 2.41 +/- 0.35 microm), but intima-media wall thickness and wall-to-lumen ratio were significantly increased in hypertensive patients compared with control subjects (0.268 +/- 0.032 versus 0.236 +/- 0.025 mm -P < or = .01- and 0.220 +/- 0.038 versus 0.195 +/- 0.028 -P < or = .05-, respectively). Peak hyperemic blood flow response (hypertensive patients versus control subjects: 349% versus 360% increase from baseline) and reactive hyperemic dilation (7.2% versus 7.9%) were similar in amplitude and duration in the two groups. These results suggest that wall thickening is an adaptive process that reduces wall tension in hypertensive patients while preserving a normal mechanical behavior of the radial artery. This is most likely accomplished by modification of the incremental elastic modulus of wall components rather than by a change in vascular tone.
Adult↗