[New data on experimental endotoxic shock].
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
H R Brunner
Publications and source records attributed to H R Brunner.
Lack of a role of circulating bradykinin in the blood pressure response to acute angiotensin converting enzyme inhibition in rats.
The role of circulating bradykinin in blood pressure regulation was investigated in conscious normotensive rats using a competitive antagonist of bradykinin. The acute blood pressure effect of this antagonist was also evaluated after inhibition of angiotensin converting enzyme with captopril and during simultaneous infusion of exogenous angiotensin II. No evidence was found for a role of circulating bradykinin in rats studied under normal conditions. Endogenous bradykinin seemed however involved in blood pressure control during angiotensin II infusion. Acute angiotensin converting enzyme inhibition had no influence on the blood pressure response to the bradykinin antagonist.
Angiotensin II↗
[Non-invasive methods of evaluation in hypertensive patients].
Major strides have been made, in the past few years, in the field of arterial hypertension, due to the availability of methods permitting a non-invasive, and precise evaluation, outside of the office, of the blood pressure as well as the cardiac response to chronic pressure surcharge. The devices used to record pressure profiles, in an ambulatory situation, are periodically activated, either automatically or by the patient himself. They are portable blood pressure recorders connected to a conventional inflatable arm cuff. The arterial blood pressure thus measured may be quite different from that measured by a physician. The value of the arterial blood pressure recorded in ambulatory is not predictable on the basis of the values obtained in a medical environment. An important factor is that the risk of cardiovascular complication seems to be better correlated to the blood pressure measurements obtained in the usual patient's environment than to those taken by the physician. Sonocardiography is another non-invasive method allowing a better screening of the patients likely to benefit from an antihypertensive treatment. A left ventricular hypertrophy may be detected quite early in an hypertensive patient. The regression of such anomaly under antihypertensive treatment permits to ascertain the good quality of the blood pressure control obtained with antihypertensive medications.
Ambulatory Care↗
[ACE inhibitors and their clinical significance].
With the availability of orally active angiotensin converting enzyme (ACE) inhibitors, it has become possible to chronically inhibit the renin-angiotensin system. When given to hypertensive patients as monotherapy, these agents can normalize the blood pressure in about 50% of all cases like other antihypertensive drugs. If the monotherapy is not sufficient to normalize blood pressure, the addition of a sodium depletion, for instance by administering concomitantly a diuretic, can become necessary to normalize blood pressure. The antihypertensive effect of ACE inhibitors is characterized by some particularly favorable features: ACE inhibitors attenuate the fall in serum potassium and the rise in plasma uric acid induced by diuretics, they do not cause any salt retention nor orthostatic hypotension, they do not raise pulse rate when they reduce blood pressure, and they certainly do not reduce the perfusion rate of the brain, the heart or the kidneys. The same features are apparent when using these agents in patients with congestive heart failure, in whom these drugs enhance cardiac output and exercise capacity by decreasing simultaneously pre- and afterload to the heart. Untoward effects of ACE inhibitors are relatively infrequent and they can mostly be foreseen based on an understanding of the pharmacological mechanisms of these compounds. Thus, with appropriate use, untoward effects are often completely avoided. Recent clinical studies have suggested that ACE inhibitors, when compared to other antihypertensive drugs, can improve the quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin-Converting Enzyme Inhibitors↗
[Management of the multiple organ donor].
Explore the source record for details and available documents.
Brain Death↗
Nicotine-induced release of vasopressin in the conscious rat: role of opioid peptides and hemodynamic effects.
Nicotine has been shown to stimulate the release of vasopressin and to cause significant hemodynamic changes. The mechanisms leading to enhanced vasopressin secretion and the vascular consequences of the high plasma vasopressin levels during nicotine infusion have not yet been determined. Therefore, the purposes of the present study were 1) to examine in normal conscious rats the role of opioid peptides in the nicotine-induced increase in plasma vasopressin levels and 2) to assess the role of vasopressin in the hemodynamic effects of nicotine (20 micrograms/min for 15 min) using a specific V1 antagonist of the vascular actions of vasopressin. Plasma vasopressin levels were significantly increased in the nicotine-treated animals (39.5 +/- 10 vs. 3.7 +/- 0.6 pg/ml in the controls, P less than .01). Pretreatment with naloxone, an antagonist of opioids at their receptors, did not reduce the vasopressin levels (47.7 +/- 9 pg/ml). Nicotine also increased mean blood pressure (122.5 +/- 2.5 to 145.2 +/- 3.3 mm Hg, P less than .01) and decreased heart rate (461 +/- 6 to 386 +/- 14.5 beats/min, P less than .05). Administration of the vasopressin V1 antagonist before the nicotine infusion did not affect the systemic hemodynamics or the regional blood flow distribution, as assessed by radiolabeled microspheres. Thus, these results suggest that the nicotine-induced secretion of vasopressin is not mediated by opioid receptors and that the high plasma vasopressin levels do not exert any significant hemodynamic effect on cardiac output or blood flow distribution.
Animals↗
Neuropeptide Y normalizes renin secretion in adrenalectomized rats without changing blood pressure.
In the periphery, neuropeptide Y is present in plasma, in the adrenal medulla as well as in sympathetic nerve endings and in the juxtaglomerular apparatus. The aim of the present study was to assess the effect of this peptide on renin secretion. Normotensive rats were adrenalectomized or sham-operated and made hypertensive with methylprednisolone acetate (20 mg/kg s.c. once weekly). Deoxycorticosterone pivalate (10 mg/kg s.c. once weekly) was also given to prevent mineralocorticoid deficiency. Two weeks after initial surgery, 12 adrenalectomized and 8 sham-operated conscious rats were infused for 30 min with neuropeptide Y (0.1 micrograms/min) whereas 8 other adrenalectomized and 9 sham-operated conscious rats received under similar conditions the vehicle of neuropeptide Y (10 microliter/min). Neither before nor during the infusions was there a significant difference in blood pressure and heart rate between the 4 groups of animals. Plasma renin activity, measured at the end of the infusion, was 30.5 ng/ml/hr in the adrenalectomized group receiving vehicle and 6.3 ng/ml/hr in that infused with neuropeptide Y (p less than 0.001). This latter value did not differ from that found in sham-operated rats. These results suggest that neuropeptide Y may play an important role in regulating renin secretion.
Adrenalectomy↗
[Effects of perfusion of human atrial natriuretic factor in normal volunteers].
The renal and systemic effects of a synthetic atrial natriuretic peptide (ANP) corresponding to the sequence of the human hormone was investigated in normal volunteers. Each subject was infused for 4 hours on 3 different days at a one week interval with either ANP (0.5 or 1 microgram/min) or its vehicle. ANP enhanced natriuresis without simultaneously modifying glomerular filtration rate. ANP did, however, reduce effective renal plasma flow. In spite of the increased natriuresis, the activity of the renin-angiotensin-aldosterone system was reduced during ANP infusion. ANP induced a transient increase in skin blood flow. No change in blood pressure and heart rate occurred in the course of the experiment.
Adult↗
[Vasopressin in acute myocardial infarct: clinical implications].
Since current data on vasopressin (AVP) secretion during the early phase of myocardial infarction is not extensive, plasma AVP was measured in 26 patients with acute myocardial infarction. Twelve had an increased AVP concentration (23.2 +/- 7.0 pg/ml; mean +/- SEM) whereas 14 had an AVP level less than 3 pg/ml (1.96 +/- 0.14 pg/ml). The patients with AVP greater than 3 pg/ml had higher heart rate and plasma osmolality than those with AVP less than 3 pg/ml. Blood pressure values were the same in both groups of patients. There was no difference in peak CPK and iso CPK activities between the two groups. Seven patients with AVP greater than 3 pg/ml died within the next few days, while only 1 patient with AVP less than pg/ml died. It thus appears that increased AVP concentration during acute myocardial infarction is associated with a poor prognosis. Whether it is a cause or a consequence of an unfavourable course of myocardial infarction remains to be determined.
Adult↗
The hemodynamic response of conscious normotensive rats to atriopeptin III: Lack of a role of the parasympathetic nervous system.
The influence of the parasympathetic nervous system on the cardiovascular response to a synthetic atrial peptide (atriopeptin III) was examined in conscious normotensive rats by utilizing radiolabelled microspheres. Atriopeptin III was infused intravenously for 30 min at a rate of 1 microgram/min per rat in animals pretreated with a bolus intravenous injection of atropine, (150 micrograms/rat, n = 8) or of its vehicle (n = 8). Additional animals (n = 9) received the vehicle of both atropine and atriopeptin III. The atrial peptide decreased mean blood pressure to a similar extent in rats pretreated with atropine (from 124 +/- 4.5 to 108 +/- 5.3 mm Hg, mean +/- S.E.M., P less than 0.05) and in the controls (from 123 +/- 3.8 to 105 +/- 3.8 mm Hg, P less than 0.05). Heart rate rose significantly after administration of atropine. After the 30 min infusion, the cardiac index was significantly lower (P less than 0.05) in both groups infused with atriopeptin III (23.7 +/- 2.3 after atropine pretreatment and 25.1 +/- 2.2 ml X min-1 X 100 g-1 without atropine) than in the group of rats given only the vehicle of both atropine and atriopeptin III (32.4 +/- 2.8 ml X min-1 X 100 g-1). Calculated systemic vascular resistance tended to be higher in the former two groups than in the latter. There was no significant difference in regional blood flow distribution within the three groups of rats. These data therefore indicate that in conscious rats atriopeptin III reduces blood pressure and cardiac output without concomitantly diminishing total peripheral vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Prognostic value of the renin-angiotensin system in response to salt restriction and prognosis of alcoholic ascitic cirrhosis].
Prognostic factors in alcoholic cirrhosis with ascites were analyzed in a prospective study of 37 patients (25 men, 12 women), 26 of whom presented with clinically diagnosed ascites. A good therapeutic response following salt restriction was obtained in 50%; this response correlated well with an initially small ascites volume, male sex, daily urinary sodium excretion of greater than 10 mmol, plasma renin activity of less than 5 ng/ml/hr and a normal plasma aldosterone level. On the other hand, age, number of episodes and duration of ascites, hepatic functional parameters, plasma creatinine concentration and portal venous pressure had no predictive value as to therapeutic response. Patients' survival was inversely related to plasma renin activity and positively to sodium excretion. The one-year mortality rate reached 88% in patients with renin of greater than 5 ng/ml/hr or daily urinary sodium excretion of less than 10 mmol, while 70% of patients with renin of less than 5 ng/ml/hr or daily sodium excretion of greater than 10 mmol survived more than two years. No prognostic index of survival could be derived from age, sex, number of episodes, duration and volume of ascites, portal venous pressure or hepatic biochemical parameters. Thus, in cirrhotic alcoholic patients with ascites the determination of daily urinary sodium excretion, which is inversely related to the activity of the renin-angiotensin system, provides a useful prognostic index for the response to salt restriction and longterm survival.
Adult↗
Pharmacokinetics and pharmacodynamics of pentopril, a new angiotensin-converting-enzyme inhibitor in humans.
In a single, ascending-dose tolerance study, nine healthy volunteers were given oral pentopril 50 to 750 mg (CGS 13945) in groups of three each. Disposition characteristics of pentopril and its active metabolite (CGS 13934) were determined using plasma concentration and urinary excretion data. The drug was absorbed rapidly following zero-order kinetics. The drug has an apparent volume of distribution of 0.83 L/kg and an oral clearance of about 0.79 L/hr/kg. Urinary excretions, calculated after 125- and 250-mg doses, showed a dose proportional urinary recovery of 21% (+/- 5%) for pentopril and 40% (+/- 5%) for CGS 13934. In the multiple-dose study of 125 mg orally q12h in six healthy subjects, the plasma concentrations for both drug and metabolite showed no appreciable accumulation of either compound, which was expected from their short pharmacokinetic half-lives (pentopril, less than 1 hr; CGS 13934, approximately 2 hr). In a separate pharmacodynamic study, drug and metabolite concentrations were evaluated against angiotensin-I (AI)-induced changes in blood pressure and plasma angiotensin-converting-enzyme (ACE) activity in healthy volunteers after single oral doses (range, 10-500 mg). The pharmacodynamic half-life for plasma ACE inhibition increased with the dose (10 mg, 1.5 hr; 500 mg, 9.8 hr). There was a close relationship between the plasma level of the metabolite and the inhibition of plasma ACE activity and AI-induced pressor response. A hyperbolic function adequately described the dependence of plasma ACE activity on plasma metabolite concentration with a concentration at half-maximal inhibition of 53 ng/mL.
Administration, Oral↗
Atrial natriuretic peptides: reproducibility of renal effects and response of liver blood flow.
To assess the variability of the response to exogenous atrial natriuretic peptide (ANP), it was infused at the rate of 1 microgram/min for 2 h in 6 salt-loaded normal volunteers under controlled conditions on 2 occasions at an interval of 1 week. The effect on solute excretion and the haemodynamic and endocrine actions were highly reproducible. The constant ANP infusion caused a delayed and prolonged excretion of sodium, chloride and calcium, no change in potassium or phosphate excretion or in glomerular filtration rate but a marked decrease in renal plasma flow. Blood pressure, heart rate and the plasma levels of angiotensin II, aldosterone, arginine vasopressin and plasma renin activity were unaltered. The effect of a 2-h infusion of ANP 0.5 microgram/min or its vehicle on apparent hepatic blood flow (HBF) was also studied in 14 normal volunteers by measuring the indocyanine green clearance. A 21% decrease in HBF was observed in subjects who received the ANP infusion (p less than 0.01 vs vehicle). Thus, ANP infused at a dose that did not lower blood pressure decreased both renal and liver blood flow in normotensive volunteers. The renal and endocrine responses to ANP were reproducible over a 1-week interval.
Adult↗
Single and repeated dosing of the converting enzyme inhibitor perindopril to normal subjects.
The new orally active angiotensin converting enzyme (ACE) inhibitor perindopril (S9490-3) was evaluated in 18 normotensive men. In three subjects the pressor response to exogenous angiotensin I was tested. A 8 mg oral dose reduced the pressor response by greater than 80%. Single oral perindopril doses of 2, 4, 8, and 16 mg were given to groups of five subjects each. Eight and 16 mg decreased plasma ACE activity within 4 hours to less than 10% of control; 72 hours later, plasma ACE activity was still reduced by at least 40%. Doses of 4 and 8 mg po once a day were then given for 8 days to two groups of six subjects. Four hours after the first and the last morning doses, plasma angiotensin II, aldosterone, and plasma ACE activity fell significantly, whereas blood angiotensin I and plasma renin activity rose. There was no evidence of drug accumulation. No significant change in blood pressure or heart rate was observed. Thus in normotensive subjects, perindopril seems an effective, orally active, long-lasting ACE inhibitor.
Acetylcholinesterase↗
Dopaminergic control of aldosterone secretion in hypertensive patients chronically treated with an angiotensin converting enzyme inhibitor.
To investigate whether dopamine plays a role in the regulation of aldosterone secretion during long-term blockade of the renin-angiotensin system, we studied the effect of metoclopramide, a competitive antagonist of dopamine, in 6 patients with essential hypertension chronically treated with the angiotensin converting enzyme inhibitor enalapril. All but one of these patients received a diuretic in addition to enalapril. Six hours after the daily morning dose of enalapril (10-40 mg p.o.) a 10 mg bolus dose of metoclopramide was injected intravenously. In one patient a hypotensive episode developed following metoclopramide administration. In the 5 other patients plasma aldosterone significantly rose within 30 min after metoclopramide from 51 +/- 8.7 to 128.2 +/- 29.2 pg/ml. This metoclopramide-induced release of aldosterone occurred in the absence of concomitant changes in circulating angiotensin 11, potassium and ACTH levels. Metoclopramide given during chronic blockade of the renin-angiotensin system caused anxiety and agitation in 2 patients. The increase in plasma aldosterone following competitive dopamine blockade in the face of chronic angiotensin converting enzyme inhibition, unchanged plasma potassium and ACTH levels strongly suggests that in hypertensive patients, dopamine exerts a direct inhibitory effect on aldosterone secretion.
Adrenocorticotropic Hormone↗
Octapeptide-specific and sensitive assay for angiotensin II in plasma.
Angiotensin-(1-8)octapeptide (angiotensin II) is the active principle of the renin-angiotensin system. Crossreaction of angiotensin II-antisera with inactive precursors and metabolic fragments prevented the specific quantitation of this hormone in biological fluids. Peptide-extraction on bonded-phase silica followed by peptide-separation using isocratic reverse-phase high performance liquid chromatography and subsequent radioimmunoassay rendered possible the octapeptide-specific measurement of angiotensin II in 2 ml plasma with a detection limit of 0.4 fmol/ml. The coefficient of variation for intra-assay precision was 0.06 and for inter-assay precision 0.13. 125I-angiotensin II was recovered from plasma by solid-phase extraction to 99 +/- 2% (mean +/- S.D.). The overall recovery of 5, 10 and 20 fmol unlabeled angiotensin II added to plasma was 80 +/- 10%. Plasma concentrations in supine normal humans averaged 4.1 +/- 1.6 fmol/ml and were suppressed below the detection limit by angiotensin I converting enzyme inhibition.
Angiotensin II↗
Double-blind comparison of the cardioselective beta-blockers bisoprolol and atenolol in hypertension: the Bisoprolol International Multicenter Study (BIMS).
The antihypertensive efficacy and tolerability of bisoprolol and atenolol were compared in the Bisoprolol International Multicenter Study (BIMS). In 104 patients with essential hypertension (21 to 70 years of age and diastolic blood pressures (DBP) of 100-120 mm Hg in the sitting position), after a four-week placebo period, the active drug was given in a random double-blind crossover design (10 to 20 mg bisoprolol, 50 to 100 mg atenolol) for eight weeks each, with a 2 to 6 week placebo wash-out phase between active therapy. All blood pressures were recorded 24 h after drug intake. Of the 104 patients, 10 were withdrawn during the study because of unwanted effects, unsatisfactory blood pressure response, or intercurrent disease, leaving 94 for intraindividual comparisons. After 8 weeks active treatment with individually titrated dose, there were slightly, but significantly greater falls in blood pressure with bisoprolol (p less than or equal to 0.05). Diastolic target pressures of less than or equal to 95 mm Hg were reached in 68% with bisoprolol and 56% with atenolol (p less than or equal to 0.05; Mc Nemar). There was no between treatment group difference in the patients' self-assessed well-being. For both drugs, response rates were greater in patients below the age of 60 years than in those above 60 years. Better antihypertensive responses were observed with bisoprolol in patients regularly smoking cigarettes.
Adrenergic beta-Antagonists↗
Chronic treatment of hypertensive patients with converting enzyme inhibitors.
It is widely accepted that pharmacologic reduction of the blood pressure of hypertensive patients reduces the risk of at least some of the major cardiovascular complications (1-5). All major studies were carried out before orally active converting enzyme inhibitors had become available. In other words, very effective antihypertensive drugs have been around for quite some time and have already proven their efficacy. Therefore, the considerable enthusiasm that has developed during the very recent years for the new converting enzyme inhibitors should be evaluated in the light of previously available antihypertensive drugs, the more so, as drugs cheaper than converting enzyme inhibiting agents are presently available. Thus, the increased expense when using this new class of antihypertensive compounds should be justified by a therapeutic gain. When evaluating a class of antihypertensive drugs such as converting enzyme inhibitors, there are basically three main considerations: What is their efficacy in long-term use? This includes the effect on blood pressure, on heart, on hemodynamics, and on blood flow distribution. What are the metabolic effects? What is the effect on sodium and potassium excretion? How are the serum lipids affected by its use? Are there any untoward effects related either to the chemical structure of the compound per se or rather to the approach? In particular, are there any central effects of the drug which can cause discomfort to the patient? The following discussion has the principal aim to review these aspects with chronic use of oral converting enzyme inhibiting agents without, however, even attempting to provide an exhaustive review of the subject.
Angiotensin I↗