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Biomedical subjects

H R Brunner

Publications and source records attributed to H R Brunner.

At least 19 recordsLinked to original sources
PubMed1992

[What have we learned from converting enzyme inhibitors on renin-angiotensin system?].

Angiotensin-converting-enzyme (ACE) inhibitors are now widely used to treat patients with high blood pressure or heart failure. The favourable results obtained with these inhibitors of the renin-angiotensin system suggest that angiotensin II has a noxious effect on the development and/or course of these diseases. ACE inhibitors are usually well tolerated. Their most severe side-effects are mostly foreseeable and therefore avoidable. Chronic blockade of the renin-angiotensin system increasingly seems to be a good therapeutic approach to the protection of the vital organs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

[Evaluation of the antihypertensive efficacy of isradipine SRO as assessed by ambulatory blood pressure determination].

The calcium channel blocker isradipine has become recently available in a form with delayed release (isradipine SRO). The anti-hypertensive efficacy and tolerance of this preparation at a single daily dose of 5 mg was studied in 40 patients with uncomplicated essential hypertension over a period of 6 weeks. Blood pressure during office visits decreased under Isradipine SRO from 164/105 +/- 16/7 to 144/93 +/- 12/7 mmHg (mean +/- 1 standard deviation p < 0.001). Using ambulatory blood pressure recording we could show that antihypertensive efficacy of the new galenic form persisted over 24 hours. During the day the blood pressure dropped from 150/95 +/- 13/7 to 141/91 +/- 13/7 mmHg (p < 0.001), during the night from 131/85 +/- 13/3 to 121/81 +/- 15/9 mmHg (p < 0.001). Heart-rate was not changed by treatment and the drug was well tolerated. Isradipine SRO at a single dose is thus well suited for antihypertensive treatment.

Adult↗
PubMed1992

Trandolapril in hypertension: overview of a new angiotensin-converting enzyme inhibitor.

Trandolapril is a new angiotensin-converting enzyme (ACE) inhibitor that has been extensively investigated in vitro, in animals, in normal volunteers, and in hypertensive patients. It has been shown to exert all the effects typical for the class of ACE inhibitors, and has a marked impact on the reversal of structural hypertrophy of the myocardium and the arterial wall. Trandolapril is a prodrug that must be hydrolyzed to its active metabolite, trandolaprilat. This latter compound exhibits a particularly high affinity for converting enzyme, which results in a slow dissociation and one of the longest durations of action of any converting enzyme inhibitor known so far. Trandolapril reduces blood pressure consistently throughout the 24-hour period following intake. Accordingly, trandolapril, more than any other drug of its class, can be considered a true, once-a-day antihypertensive drug.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Endothelial function in chronic congestive heart failure.

There is evidence that the endothelium plays an important role in the control of human vascular tone by releasing endothelium-derived nitric oxide. The hypothesis that an impairment of this mechanism is involved in the increased peripheral vasoconstriction of patients with chronic congestive heart failure (CHF) was tested. Acetylcholine and N-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthesis from L-arginine, were infused in the brachial artery of healthy volunteer subjects (controls) and patients with severe CHF. The radial artery diameter was determined by a high-precision A-mode ultrasound device, using a 10 MHz probe. Forearm blood flow was calculated from vessel diameter and blood flow velocity measured simultaneously by Doppler. The blood flow response to acetylcholine was blunted in patients with CHF compared with that in control subjects. In contrast, the decrease in blood flow induced by L-NMMA was exaggerated in CHF, and the blood flow response to nitroglycerin was preserved. The changes in radial artery diameter induced by acetylcholine and L-NMMA were not significant in control subjects and CHF patients, but dilation of the radial artery by nitroglycerin was significantly reduced in CHF. The results demonstrate an impaired endothelium-dependent dilation of forearm resistance vessels in CHF, suggesting a reduced release of nitric oxide on stimulation. In contrast, the basal release of nitric oxide from endothelium of forearm resistance vessels is preserved or may even be enhanced, and may play an important compensatory role in chronic CHF by antagonizing neurohumoral vasoconstrictor forces in CHF.

Acetylcholine↗
PubMed1992

[Preliminary evaluation of the Profilomat, a new portable blood pressure recorder].

Ambulatory blood pressure monitoring is increasingly used in clinical evaluation of the hypertensive patient. The aim of the present study is to investigate the accuracy of non-invasive blood pressure measurements provided by the Profilomat, a new portable, automatic blood pressure recorder, in normotensive subjects and hypertensive patients. The results showed a good correlation between the blood pressure values measured by this apparatus and those determined simultaneously by the conventional auscultatory method (sphygmomanometer). Thus, the Profilomat appears to be a useful instrument for study of arterial blood pressure outside the doctor's office.

Adult↗
PubMed1992

[Practical consequences blood pressure variability].

Arterial pressure varies over the course of the day depending on activities. It increases frequently in the presence of the physician. Long term blood pressure recording makes available a multitude of measurements taken during usual activities of the patient. These measurements permit identification of hypertensive patients at high risk i.e. patients with high blood pressure not only when facing their physician.

Blood Pressure↗
PubMed1992

[The treatment of arterial hypertension: which drug for which patient?].

Hypertension is a multifactorial disease. Various antihypertensive drugs can lower arterial pressure in a given patient in a more or less efficient way. The sequential testing of several drugs is most promising for lowering blood pressure by monotherapy. If necessary a drug combination is preferable to dose adjustments of a single substance because of the risk for side effects growing with the dose.

Algorithms↗
PubMed1992

Drug concentration response relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist.

The aim of this study was to investigate the relationships between plasma concentrations of losartan, an orally active angiotensin II inhibitor, its active metabolite EXP3174, and angiotensin II blockade. Six healthy subjects received single oral doses of 40, 80, or 120 mg losartan and placebo at 1-week intervals in a crossover study. Angiotensin II blockade was assessed by the blood pressure response to exogenous angiotensin II before and after losartan administration. EXP3174 reached higher plasma concentrations and was eliminated more slowly than its parent compound; its levels paralleled the profile of angiotensin II blockade closer than losartan. Inhibition of the pressure response was dose dependent. The Hill-shaped relationship between response and EXP3174 concentration (or time-integrated variables) approached a plateau with 80 mg. The dose-dependent increase in plasma renin and angiotensin II exhibited a considerable individual scatter. We conclude that losartan produces a dose-dependent, effective angiotensin II blockade that is largely determined by the active metabolite EXP3174.

Administration, Oral↗
PubMed1992

Clinical experience with angiotensin II receptor antagonists.

This series of studies was designed to assess in normal volunteers the relationships between various doses (5, 10, 20, 40, 80, and 120 mg) of the orally active angiotensin II antagonist losartan (DuP 753, MK-954) and their inhibitory effect on the pressure response to a given bolus of angiotensin I or II. It was found that the maximal inhibitory effect was reached with a dose of 80 mg. The minimal dose necessary for maximal efficacy would therefore be expected to be between 40 and 80 mg. The effect lasted for more than 24 h and was related almost exclusively to the circulating levels of the active metabolite EXP3174. It remains to be demonstrated in hypertensive patients that the same dose relationship holds for the antihypertensive effect, but preliminary data already suggest that this is the case.

Administration, Oral↗
PubMed1992

Measurement of converting enzyme activity by antibody-trapping of generated angiotensin II. Comparison with two other methods.

Activity of the angiotensin converting enzyme (ACE) is usually measured in vitro by estimation of products cleaved by the enzyme from synthetic substrates. These substrates have affinities for ACE different from the natural substrate angiotensin I, and insensitive detection systems necessitate millimolar substrate concentrations while physiological angiotensin I concentrations are in the picomolar range. A new assay for ACE activity measurement was developed which reliably quantitates femtomoles of generated angiotensin II in plasma from angiotensin I added at a 17 pmol/mL concentration. The production of high affinity monoclonal antibodies against angiotensin II (Kd = 7 x 10(-11) mol/L) allowed a quantitative trapping (and thus protection from degrading enzymes) of angiotensin II generated during the incubation step and subsequent radioimmunoassay by simple dilution with labelled angiotensin II. Using 40 microL plasma, the detection limit was 20 fmol/mL/min. Normal human plasma has an ACE activity of 335 +/- 83 fmol/mL/min (mean +/- SD). Precision was characterized by coefficients of variation of less than or equal to 11% both within-assay and between-assays. Accuracy of the new method was established by comparing ACE activity with the ratio of plasma angiotensin II/angiotensin I in plasma obtained from normal volunteers 0.5 to 24 h after oral administration of 20 mg enalapril. The percentage of ACE inhibition indicated by both methods was almost identical (r = 0.93, n = 60, P less than .001). Since the latter ratio appears to reflect in vivo ACE activity, these results indicate that accurate measurement in vitro of ACE activity in vivo has been achieved.

Administration, Oral↗
PubMed1992

Neurohormonal consequences of diuretics in different cardiovascular syndromes.

Diuretics have long been used to lower blood pressure in hypertensive patients or to control body fluid and electrolyte homeostasis in diseases such as congestive heart failure, chronic renal failure or cirrhosis. The initial response to diuretics is a negative sodium and fluid balance. The diuretic-induced loss of salt and water activates several hormonal systems such as vasopressin, the renin-angiotensin-aldosterone system or the sympathetic nervous system which tend to compensate for the changes in sodium and water balance. This neurohormonal response may have important clinical implications. Thus, the activation of the renin-angiotensin-aldosterone cascade appears to be partially responsible for the flat dose-blood pressure response curve of thiazides in hypertensive patients. It may also be responsible for the difference between responders and non-responders to diuretic therapy and for the development of side-effects such as hypokalaemia, metabolic alkalosis or hyponatraemia. There are several ways to prevent the undesirable consequences of the neurohormonal responses to diuretics. The first is to use low doses of these agents. It is also possible to combine them with agents that block the activity of the renin-angiotensin-aldosterone system such as ACE inhibitors or in combination with drugs that reduce aldosterone secretion such as calcium antagonists. The development of drugs able to enhance urinary sodium excretion and to reduce simultaneously the activity of the renin-angiotensin-aldosterone system may offer a new interesting alternative. This might perhaps be achieved in the future with the administration of neutral endopeptidase inhibitors which interfere with the enzymatic degradation of atrial natriuretic peptide.

Animals↗
PubMed1992

Antagonizing and measurement: approaches to understanding of hemodynamic effects of kinins.

Hemodynamic effects of the kallikrein-kinin system can be investigated by experimental administration of specific kinin antagonists and by measurement of kinin levels in the circulating blood. In conscious normal rats, the bradykinin analog B4162 blunts the hypotensive effect of exogenous bradykinin. This kinin antagonist has no blood pressure effect in control rats, but it enhances the pressor effect of vasoconstrictor substances such as vasopressin or angiotensin II when they are infused at subpressor doses. Endogenous kinins may therefore participate in blood pressure regulation by antagonizing pressor substances. Plasma levels of endogenous kinins are normally in the low picomolar range. They are rapidly generated and destroyed in biological fluids. Thus, measurement of plasma kinins requires sensitive assays based on high-affinity antibodies and careful sample-handling techniques. Nonpolar solid-phase extraction on phenylsilylsilica provides a rapid, reliable, and easy extraction of kinins from plasma with constant and high recoveries.

Amino Acid Sequence↗
PubMed1992

Inhibitory effect of neuropeptide Y on stimulated renin secretion of awake rats.

1. (1-36)-NPY is a vasoconstrictor peptide widely distributed in sympathetic nerve terminals. This peptide exerts an inhibitory action on renin release induced by various stimuli. Post-synaptic neuropeptide Y (NPY) receptors show a high affinity for (1-36)-NPY as well as for the agonist (Pro34)-NPY, while presynaptic receptors bind preferentially (13-36)-NPY. 2. This study was undertaken to assess whether the NPY induced renin suppression in awake normotensive rats infused with the beta-adrenoceptor stimulant isoproterenol is mediated by activation of pre- or post-synaptic receptors. 3. Non-pressor doses of (1-36)-NPY and (Pro34)-NPY markedly attenuated the renin secretion triggered by isoproterenol whereas (13-36)-NPY had no effect. This suggests that the effect of NPY on renin release is due to the stimulation of post-synaptic receptors. However it remains unknown whether NPY acts directly on juxtaglomerular cells or indirectly by modifying intraglomerular haemodynamics.

Animals↗
PubMed1992

Ambulatory blood pressure monitoring as a means to avoid overtreatment of elderly hypertensive patients.

Do elderly similarly to younger hypertensive patients tend to be overtreated if therapeutic decisions are based exclusively on blood pressure measured by the physician in his office? Eighteen hypertensive patients (10 previously treated) aged 70 years or more had repeatedly office systolic blood pressure greater than or equal to 170 mm Hg and/or diastolic blood pressure greater than or equal to 100 mm Hg. The physicians in charge were asked to reduce blood pressure within 4 months to a target of less than or equal to 160/95 mm Hg using any drug regimen. Blood pressure was monitored during daytime using a noninvasive blood pressure recorder, but the results of the recording were not available to the physicians until the end of the study. At the outset, 11 patients had a mean ambulatory recorded blood pressure less than 170/100 mm Hg. Those patients who exhibited high blood pressures only in the doctor's presence did not reduce their ambulatory blood pressure when antihypertensive therapy was initiated or intensified in order to reduce office blood pressure. This contrasted with the significant fall in ambulatory blood pressure observed in the presence of the doctor. Thus ambulatory blood pressure monitoring seems useful to avoid overtreatment not only of younger but also of elderly hypertensive patients.

Aged↗
PubMed1992

Conduit artery compliance and distensibility are not necessarily reduced in hypertension.

The goal of this study was to investigate whether the elastic behavior of conduit arteries of humans or rats is altered as a result of concomitant hypertension. Forearm arterial cross-sectional compliance-pressure curves were determined noninvasively by means of a high precision ultrasonic echo-tracking device coupled to a photoplethysmograph (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring. Seventeen newly diagnosed hypertensive patients with a humeral blood pressure of 163/103 +/- 4.4/2.2 mm Hg (mean +/- SEM) and 17 age- and sex-matched normotensive controls with a humeral blood pressure of 121/77 +/- 3.2/1.9 mm Hg were included in the study. Compliance-pressure curves were also established at the carotid artery of 16-week-old anesthetized spontaneously hypertensive rats (n = 14) as well as Wistar-Kyoto normotensive animals (n = 15) using the same echo-tracking device. In these animals, intra-arterial pressure was monitored in the contralateral carotid artery. Mean blood pressures averaged 197 +/- 4 and 140 +/- 3 mm Hg in the hypertensive and normotensive rats, respectively. Despite the considerable differences in blood pressure, the diameter-pressure and cross-sectional compliance-pressure and distensibility-pressure curves were not different when hypertensive patients or animals were compared with their respective controls. These results suggest that the elastic behavior of a medium size muscular artery (radial) in humans and of an elastic artery (carotid) in rats is not necessarily altered by an increase in blood pressure.

Animals↗