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Biomedical subjects

H R Brunner

Publications and source records attributed to H R Brunner.

At least 109 records · Page 6Linked to original sources
PubMed1996

Volemic status influences the response of plasma atrial natriuretic factor to positive airway pressure.

UNLABELLED: STUDY OBJECTIVE; To evaluate interactive effects of volemic status and positive end-expiratory pressure (PEEP) on the plasma levels of atrial natriuretic factor (ANF) in assist-controlled mechanical ventilation (MV). DESIGN: Three successive protocols applied in randomized order to each participant. SETTING: Clinical investigation laboratory. PARTICIPANTS: Twenty-one young, healthy adults. INTERVENTIONS: The three protocols were as follows: (1) MV+PEEP, normovolemia; (2) MV+PEEP, hypervolemia; and (3) spontaneous breathing (SB), hypervolemia. In protocols 1 and 2, a preliminary period of SB lasting 2 h was followed by MV alone (0.5 h), MV+20 cm H2O PEEP (1 h), and a recovery period of SB (1.5 h). Hypervolemia was induced by the continuous i.v. infusion of 3 L of 0.9% NaCl in 5 h (protocols 2 and 3). MEASUREMENTS AND RESULTS: Heart rate, BP, and the plasma levels of immunoreactive ANF and catecholamines were measured serially. During hypervolemia, ANF significantly decreased when PEEP was added to MV (protocol 2: from 31.1 +/- 2.7 to 20.7 +/- 1.5 fmol/mL; p < 0.01). This did not occur in normovolemia (protocol 1: from 20.0 +/- to 16.7 +/- 1.2 fmol/mL; p = NS). The different effects of MV+PEEP in normovolemia and hypervolemia were not related to differences in circulating catecholamine levels. CONCLUSIONS: These results demonstrate for the first time (to our knowledge) that volemic status modulates the response of plasma ANF to PEEP in humans. The role of ANF in the water and salt retention induced by MV with PEEP might be limited to hypervolemic conditions.

Adult↗
PubMed1996

Experience with angiotensin II antagonists in hypertensive patients.

1. The availability of orally active specific angiotensin receptor antagonists (AT1 antagonists) has opened new therapeutic choices and provided probes to test the specific role of the renin-angiotensin system in the pathogenesis of cardiovascular disease. 2. The data available so far suggest that the antihypertensive efficacy of angiotensin receptor antagonists is comparable to that of angiotensin-converting enzyme (ACE) inhibitors. This provides further evidence that this latter class of drugs exerts its effect mainly through blockade of the renin-angiotensin enzymatic cascade. As expected, the association of a diuretic exerts an equally strong additive effect to the antihypertensive efficacy of both classes of drugs. 3. The most common side effect of ACE inhibitors, dry cough, does not occur with AT1 antagonists, which confirms the long-held view that this untoward effect of the ACE inhibitors is due to renin-angiotensin-independent mechanisms. 4. Long-term studies with morbidity/mortality outcome results are needed, before a definite position can be assigned to this newcomer in the orchestra of modern antihypertensive drugs. Notwithstanding, this new class of agents already represents an exciting new addition to our therapeutic armamentarium.

Angiotensin II↗
PubMed1996

Renal effects of angiotensin II receptor blockade and angiotensin-converting enzyme inhibition in healthy subjects.

The evaluation of a new drug in normotensive volunteers can provide important information, as long as the compound has a specific mechanism of action which can be evaluated in healthy subjects as well as in patients. The purpose of the present paper is to review the renal effects of new specific angiotensin II receptor antagonists observed in normotensive subjects and to compare them to those of angiotensin-converting enzyme (ACE) inhibitors. Blockade of the renin-angiotensin system with ACE inhibitors and angiotensin II antagonists induces an expected increase in plasma renin activity and plasma angiotensin I levels. Plasma angiotensin II levels decrease with ACE inhibitors, whereas they increase with angiotensin II receptor blockade. So far, the expected decrease in plasma aldosterone levels has been difficult to demonstrate with most angiotensin II antagonists. In normotensive subjects, ACE inhibitors, as well as angiotensin II antagonists, cause no change in glomerular filtration rate and either no modification or an increase in renal blood flow. Both approaches to block the renin-angiotensin system are natriuretic, and the natriuresis is more pronounced in salt-depleted subjects. Finally, in contrast to ACE inhibitors and other angiotensin II receptor antagonist, losartan markedly increases uric acid excretion and lowers plasma uric acid levels. This unique property of losartan is due to a direct interference of losartan with the uric acid transport system in the proximal tubule. The data obtained in normal subjects therefore suggest that ACE inhibitors and angiotensin II receptor antagonists have comparable renal properties. Whether this is also true in hypertensive patients and in patients with proteinuria and chronic renal failure remains to be demonstrated.

Angiotensin Receptor Antagonists↗
PubMed1995

[Diagnosis and treatment of hypertensive emergencies].

In hospital as well as in the office, the physician is often confronted with clinical situations in which blood pressure values are very high. In each case, he will have to evaluate rapidly the degree of emergency and the need for immediate antihypertensive therapy. In the last few years, the therapeutic approach to some hypertensive emergencies has changed. The purpose of the present article is to review: 1) the clinical situations where immediate control of blood pressure is necessary, 2) the present therapeutic approaches and 3) the cardiac and cerebral risks linked to an excessive and too rapid fall in blood pressure.

Adrenal Gland Neoplasms↗
PubMed1995

[Emergency and hypertensive crisis: definition and treatment].

The opinions on how fast high blood pressure values should be lowered in emergencies have changed over the last years. It seems now more and more reasonable to lower high blood pressure values over several hours rather than several minutes. In some cases, however, a rapid reduction of elevated blood pressure may be necessary. In these cases the risks of a rapid decrease of blood pressure with respect to cerebrovascular circulation have to be considered.

Acute Disease↗
PubMed1995

Beta-adrenoceptor stimulation increases neuropeptide Y release from sympathetic nerves in intact rats.

This study was undertaken to assess in conscious normotensive rats the effects of beta-adrenoceptor stimulation on plasma neuropeptide Y (NPY) levels. Wistar rats were subjected to adrenal demedullation on the right side and were either adrenalectomized or sham-operated on the left side. Eleven days later, the conscious rats were infused i.v. for 30 min with either isoproterenol (10 ng/min) or its vehicle. Plasma NPY levels were significantly lower (23.8 +/- 2.6 pM, means +/- S.E.M., n = 12, P < 0.01) in vehicle-treated medullectomized rats than in corresponding sham-operated controls (36.7 +/- 4.1 pM, n = 12). The medullectomized rats infused with isoproterenol showed plasma NPY levels (36.7 +/- 3.3 pM, n = 11) comparable to those of sham-operated rats having received the vehicle. These data therefore demonstrate that plasma NPY levels are lower in rats without adrenal medulla and that in these animals isoproterenol increases NPY release, most likely by activating pre-synaptic beta-adrenoceptors.

Adrenal Medulla↗
PubMed1995

[Noninvasive assessment of morphology and function of the great vessels].

Hypertension is well recognized as a risk factor that is associated with an increased incidence of stroke and myocardial infarction. The early detection of atherosclerosis is a real challenge and should be carried on at a cost and with a degree of risk and invasiveness that does not preclude its use in subjects with cardiovascular risk factors. For this purpose we have developed a non-invasive approach using a high resolution echotracking device making it possible to measure internal diameter and wall thickness of conduit arteries as well as their biomechanical properties. We present here a methodological overview of the system with a brief clinical study addressing the biomechanical properties of a medium size artery in hypertension as compared with normotension.

Arteries↗
PubMed1995

Beneficial clinical effect of very early enalapril treatment in patients with acute left ventricular failure complicating myocardial infarction.

Acute myocardial infarction (AMI) leads to left ventricular dysfunction, the extent of which predicts mortality. We studied the effect of very early enalapril treatment in patients with left ventricular failure (Killip classification II-III) resulting from AMI. In a double-blind randomized trial, patients on conventional treatment were started on placebo (PL, n = 15) or 2.5 mg enalapril (EN, n = 15) twice daily as early as 24 to 30 h after AMI and were followed up over a period of 21 days. One patient died in each treatment group. There were three dropouts in the placebo group (progressive heart failure requiring antiotensin-converting enzyme inhibition) and one dropout in the enalapril group (malignant ventricular arrhythmias). Plasma atrial natriuretic peptide (ANP) and norepinephrine decreased similarly in both groups from elevated baseline concentrations. The patients with the highest baseline ANP levels died in both groups: EN: 579 fmol/ml (mean 65.3 +/- 34.4 fmol/ml), PL: 403 fmol/ml (mean 63.5 +/- 37.6 fmol/ml). Killip classification improved in 9 of 13 patients on enalapril but only in 5 of 11 patients on placebo. On echocardiography an increase in fractional shortening (FS) (3.2 +/- 7.5%, p < 0.05) was found with enalapril only. Patients on placebo required more diuretics, and plasma aldosterone increased threefold. Thus, very early enalapril treatment may help prevent left ventricular failure after AMI. Extremely high initial plasma ANP concentrations may predict an unfavorable outcome.

Aged↗
PubMed1995

Studies of the renal effects of angiotensin II receptor blockade: the confounding factor of acute water loading on the action of vasoactive systems.

The acute renal tubular effects of two pharmacologically distinct angiotensin II receptor antagonists have been evaluated in normotensive volunteers on various salt diets. In the first study, the renal response to a single oral dose of losartan (100 mg) was assessed in subjects on a low (50 mmol Na/d) and on a high (200 mmol Na/d) salt intake. In a second protocol, the renal effects of 50 mg irbesartan were investigated in subjects receiving a 100 mmol Na/d diet. Both angiotensin II antagonists induced a significant increase in urinary sodium excretion. With losartan, a modest, transient increase in urinary potassium and a significant increase in uric acid excretion were found. In contrast, no change in potassium and uric acid excretions were observed with irbesartan, suggesting that the effects of losartan on potassium and uric acid are due to the intrinsic pharmacologic properties of losartan rather than to the specific blockade of renal angiotensin II receptors. Assessment of segmental sodium reabsorption using lithium as a marker of proximal tubular reabsorption demonstrated a decreased distal reabsorption of sodium with both antagonists. A direct proximal tubular natriuretic effect of the angiotensin II antagonist could be demonstrated only with irbesartan. This apparent discrepancy allowed us to reveal the importance of acute water loading as a possible confounding factor in renal studies. The results of the present analysis show that acute water loading per se may enhance renal sodium excretion and hence modify the level of activity of the renin-angiotensin system expected from a given sodium diet. Since acute water loading is a common practice in clinical renal studies, this confounding factor should be taken into account when investigating the renal effects of vasoactive systems.

Adult↗
PubMed1995

Transient inhibition of angiotensinogen production in transgenic mice bearing an antisense angiotensinogen gene.

Angiotensinogen is the precursor of the biologically active hormone angiotensin II. Enzyme kinetic parameters suggest that concentrations of plasma angiotensinogen are rate limiting in the renin reaction. It is therefore assumed that a decrease in angiotensinogen synthesis in vivo would result in a decrease in angiotensin II plasma levels and then of blood pressure. To test this hypothesis, we generated a transgenic mouse line that carries an inducible antisense angiotensinogen gene. Transient inhibition of angiotensinogen synthesis could be demonstrated in these transgenic animals. However, the amounts of liver angiotensinogen message and plasma angiotensinogen concentrations were rapidly back to levels observed in control animals.

Angiotensinogen↗
PubMed1995

Differential nitric oxide synthase activity in human platelets during normal pregnancy and pre-eclampsia.

1. Nitric oxide released from endothelial cells is a potent vasodilator that might play an important role in cardiovascular regulation during pregnancy. Platelets, like endothelial cells, contain a constitutive form of nitric oxide synthase. 2. The present study aimed to measure the activity of this nitric oxide-forming enzyme in normotensive pregnant and non-pregnant women, as well as in women who had developed pre-eclampsia. Nitric oxide synthase activity was measured in the platelets of 21 normotensive pregnant women, 16 non-pregnant women and seven pregnant women who had developed pre-eclampsia. 3. The nitric oxide synthase activity was significantly higher in normotensive pregnant women [36.8 +/- 2.7 pmol h-1 mg-1 of protein (mean +/- SEM), P < 0.001] than in non-pregnant control subjects (16.8 +/- 1.4 pmol h-1 mg-1 of protein) and in women with pre-eclampsia (24.5 +/- 2.1 pmol h-1 mg-1 of protein, P < 0.01). 4. These data suggest that nitric oxide synthesis is increased during normal pregnancy, possibly contributing to the vasodilatation associated with this condition. Nitric oxide generation, however, may be inappropriately low in pregnant women developing pre-eclampsia, thus leading to an enhanced vasoconstriction.

Adult↗
PubMed1995

Main objectives and new aspects of combination treatment of hypertension.

AIM: To review the various pharmacological approaches currently proposed for the treatment of hypertension. RESULTS: With the evolution of pharmacological treatment of hypertension, various classes of agent (diuretics, beta-blockers, angiotensin converting enzyme inhibitors, calcium antagonists and alpha 1-blockers) have become available for the initiation of antihypertensive therapy. As monotherapy, each type of agent will normalize blood pressure in about half of all hypertensive patients. Replacing one drug with another that acts through a different mechanism improves the probability of controlling blood pressure. Another way to increase the number of responders is to increase the dose; however, this often results in more side effects. A preferable way of improving efficacy is to combine low doses of drugs that have different impacts on the cardiovascular system, thus opposing the compensatory responses that tend to limit the blood pressure drop. CONCLUSION: Low-dose drug combinations are generally well tolerated and the treatment of hypertension can be simplified by using fixed-dose combinations. These combinations have the potential to become a valuable alternative in the initiation of antihypertensive therapy.

Adrenergic alpha-Antagonists↗
PubMed1995

Comparison of the angiotensin II antagonist UP269-6 with the angiotensin converting enzyme inhibitor enalapril in normotensive volunteers challenged with angiotensin I.

We assessed the inhibitory effect of UP269-6, a new orally active angiotensin II (ANG II) receptor antagonist, on the pressor action of exogenous ANG I in healthy male volunteers maintained on an unrestricted sodium intake and compared it with that of enalapril. Seven different single doses of UP269-6 ranging from 5 to 180 mg, 20 mg enalapril, or placebo were administered to 16 subjects in a double-blind fashion. The order of placebo and enalapril was randomized, and UP269-6 was given in an ascending dose order. The peak systolic blood pressure (SBP) response to a test dose of ANG I was determined serially before and after oral drug administration by monitoring finger BP by a photoplethysmographic method. No drug-related side effect was observed. There was a dose-dependent inhibition of the SBP response to the ANG I challenge. Doses as low as 40 to 80 mg had blocking effects quite similar to that of enalapril 20 mg. Ten hours after the 20- and 40-mg doses of UP269-6, the SBP response was still attenuated when drug levels no longer were measurable in plasma. UP269-6 also produced a dose-related increase in active renin and ANG II levels at 24 h after drug intake. In these volunteers on unrestricted salt intake, no statistically significant effect on 24-h urinary aldosterone excretion was observed. Based on these preliminary data, the pharmacokinetic drug half-life (t 1/2) was estimated at 4.7 h and the EC50 was estimated at 41 ng/ml. UP269-6 appears to be a well-tolerated, potent, orally active, antagonist of ANG II receptors in men. Doses of 40-80 mg might block the ANG I pressor response as does enalapril 20 mg.

Administration, Oral↗
PubMed1995

Comparison of the oral angiotensin II receptor antagonist UP 269-6 or enalapril 20 mg on blood pressure and neurohormonal effects in salt-deplete man.

We compared the response of the oral angiotensin II (Ang II) receptor antagonist (ARA) UP 269-6 with an angiotensin converting enzyme inhibitor (ACEI) enalapril 20 mg or placebo, during salt depletion in normal men. We also evaluated safety and tolerability. Sixteen healthy, normotensive male volunteers followed a standardised salt-depletion regimen for 3 days before each study day. Seven different doses of UP 269-6 (5, 10, 20, 40, 80, 120 and 180 mg) were administered double blind in a four-panel dose escalation, with enalapril and placebo randomised within each panel. Supine and erect blood pressure (BP) and heart rate (HR); serum and urinary electrolytes; plasma active renin (PAR), aldosterone, and Ang II were measured at intervals. Urinary electrolytes and aldosterone were measured for the 24 h before dosing and for 24 h after dosing. Dizziness and light-headedness on standing were reported after UP 269-6 at higher doses. Enalapril caused one episode of symptomatic postural hypotension. No other drug-related adverse events (AE) were noted. There was a dose-related decrease in supine and erect systolic and diastolic BP (SBP, DBP) with UP 269-6 at > or = 40 mg, with no change in HR. Based on the maximal decrease in mean arterial pressure (MAP), UP 269-6 at 180 mg had an effect largely comparable to that of enalapril 20 mg. There was a dose-related increase in PAR with UP 269-6. Although this was greater with UP 269-6 180 mg than with enalapril, serum and 24-h urinary aldosterone suppression was greater with enalapril than with any dose of UP 269-6.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Effects of chronic NO synthase inhibition in rats on renin-angiotensin system and sympathetic nervous system.

This study was designed to assess the role of renin and of the sympathoadrenal system in the maintenance of the hypertension induced by chronic nitric oxide synthase (NOS) inhibition in rats kept on a normal (RS) or a low-sodium (LS) diet. With the administration of NG-nitro-L-arginine methyl ester (L-NAME) in drinking water (0.4 milligrams) for 6 wk, mean intra-arterial blood pressure rose to a similar extent to 201 mmHg in the RS and 184 mmHg in the LS animals. Simultaneously, plasma norepinephrine was increased to 838 and 527 pg/ml and epinephrine to 2,041 and 1,341 pg/ml in RS and LS, respectively. Plasma neuropeptide Y levels did not change. Plasma renin activity rose to 21 ng.ml-1.h-1 in RS but remained at 44 ng.ml-1.h-1 in the LS. Both losartan (10 mg/kg) and phentolamine (0.1 mg/kg) intravenous bolus injections reduced blood pressure considerably in the L-NAME hypertensive animals. Whole brain NOS activity was reduced by 84%. Hypertension induced by chronic NOS inhibition in LS as well as in RS fed rats seems to be sustained by an interaction of several mechanisms, including the activation of the sympathetic nervous system and the renin-angiotensin system.

Amino Acid Oxidoreductases↗
PubMed1995

Simultaneous ipsilateral and contralateral measurements of vasomotion in conduit arteries of human upper limbs.

We investigated the patterns of vasomotion in various conduit arteries of the human arm. The internal diameter of the brachial, radial, ulnar, and digital artery was measured noninvasively in 17 healthy volunteers (aged 24-40 yr), using a high-precision ultrasonic echotracking device. Under resting conditions, the radial, ulnar, and digital internal diameter exhibited spontaneous oscillations (vasomotion) with a relative amplitude ranging from 1 to 5% of the mean diameter and a fundamental frequency ranging from 0.01 to 0.05 Hz. This oscillatory behavior was either quasi-periodic or irregular. The low-frequency mode (f < or = 0.05 Hz) present in the diameter signal was identified neither in the heart rate nor in the blood pressure signal. To determine whether the oscillatory activity was propagative, simultaneous measurements of diameter at two sites on the right radial artery were performed and revealed no significant consistent phase shift. Ipsilateral radial and ulnar diameters, measured at the wrist level, exhibited similar and synchronous vasomotion patterns, despite differences in the amplitude. For all subjects, contralateral measurements, performed at two symmetrical sites of the radial arteries, showed similar oscillatory patterns with a strong correlation (0.85 < r < 0.99, n = 12). These results suggested the existence of a global regulatory mechanism that coordinates vasomotion in the large conduit arteries of the human arm.

Adult↗
PubMed1995

Prevention of vascular remodelling in cardiovascular disease.

The early detection of arterial wall transformations that may further evolve into atherosclerosis may help to identify high-risk patients among the hypertensive population and to select the most appropriate treatment. Intima-media layer thickening that affects a number of hypertensive subjects may potentially represent an indicator of accelerated atherosclerotic transformation of the vessel wall. Diagnosis and quantification of these early changes preceding plaque development should make it possible to determine whether antihypertensive treatment can restore normal wall structures in addition to normalizing the blood pressure. This article reviews some of the new approaches developed in our laboratory to assess both structure and function of conduit vessels. Preliminary data suggest that it is feasible to identify minute geometrical changes in hypertensive subjects long before major vascular lesions occur. This opens a whole new field of investigation into early arterial remodelling, a potential precursor of atherosclerosis.

Adaptation, Physiological↗