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Biomedical subjects

H R Brunner

Publications and source records attributed to H R Brunner.

At least 379 records · Page 21Linked to original sources
PubMed1986

[Normalization of renin secretion by neuropeptide Y in adrenalectomized rats with glucocorticoid-induced hypertension].

In the periphery, neuropeptide Y is present in the circulation, in the adrenal medulla as well as at the level of nerve endings and of the juxtaglomerular apparatus. The aim of the present study was to assess the effect of this neuropeptide on renin secretion. Normotensive rats were biadrenalectomized 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 that initial surgery 12 adrenalectomized rats and 8 sham-operated rats were infused for 30 min with neuropeptide Y (0.1 microgram/min) whereas 8 adrenalectomized rats and 9 sham-operated rats received in similar conditions the vehicle of neuropeptide Y (10 microliters/min). At that time, the rats were conscious and there was no significant difference in blood pressure and heart rate between the 4 groups of rats. At the end of the experiment, adrenalectomized rats exhibited a markedly stimulated renin-angiotensin system. Neuropeptide Y made it possible to normalize plasma renin activity in these rats, thus suggesting that neuropeptide Y plays an important role in regulating renin secretion.

Adrenalectomy↗
PubMed1986

Regulation of renin secretion in conscious adrenalectomized rats with glucocorticoid-induced hypertension.

The effect of adrenalectomy on renin secretion was investigated in conscious rats with glucocorticoid-induced hypertension. Adrenalectomized and sham-operated rats were made hypertensive with methylprednisolone acetate (20 mg/kg s.c. once/week X 2 weeks) supplemented with deoxycorticosterone pivalate (10 mg/kg s.c. once/week X 2 weeks). During the 2 week developmental phase of hypertension, tap water or isotonic saline was given as drinking fluid to respectively 10 and 13 adrenalectomized rats and 10 and 11 sham-operated rats. On the day of the acute administration of captopril or vehicle there was no significant difference in body weight, mean blood pressure, heart rate, serum electrolytes and plasma norepinephrine levels between the 4 groups of rats. Circulating epinephrine could not be detected in adrenalectomized rats. Plasma renin activity was markedly higher in adrenalectomized rats than in the sham-operated rats even after sodium supplementation. Captopril (10 mg/kg i.v.) produced no significant blood pressure lowering effect in rats given tap water to drink, either adrenalectomized (n = 11) or sham-operated (n = 10). These findings indicate that the activation of the renin-angiotensin system in adrenalectomized rats with glucocorticoid-induced hypertension is not directly mediated by the development of adrenal failure. They also show that the maintenance of high blood pressure in this form of experimental hypertension is not significantly enhanced when renin secretion is stimulated by adrenalectomy.

Adrenalectomy↗
PubMed1986

[Usefulness of ambulatory blood pressure monitoring in hypertensive patients].

Treated or untreated hypertensive patients may have very different blood pressure levels when measured by the doctor in his surgery and when measured by ambulatory monitoring during their usual everyday activities. It is now possible to record blood pressure non-invasively with a portable blood pressure measuring device, the Remler M2000. Using this device, we observed that less than half of the patients referred by their medical practitioner for hypertension had abnormally high blood pressures during their everyday activities. We also noted that the ambulatory blood pressure profile of a given hypertensive patient cannot be predicted from the blood pressure recorded by his or her doctor. Consequently, we concluded that ambulatory blood pressure recordings would appear to be essential for the detection of patients with high blood pressure readings at the doctor's surgery and during everyday activities. These patients probably include the only group which really needs appropriate antihypertensive therapy.

Ambulatory Care↗
PubMed1986

Blockade of the vascular effect of vasopressin in patients with mild essential hypertension.

The effect of circulating arginine vasopressin (AVP) on blood pressure, heart rate and skin blood flow was investigated in 8 untreated patients with mild essential hypertension using a specific antagonist of the pressor effect of AVP. Skin blood flow was measured with a laser Doppler flowmeter and blood pressure with a Remler M2000 recorder. The study was carried out in double-blind fashion using a cross-over design. Each patient received at a 60 min interval the AVP-antagonist, d(CH2)5Tyr(Me) AVP, 5 micrograms/kg i.v., and its vehicle. The sequence of treatment phases was randomly allocated. Pretreatment plasma AVP levels averaged 1.1 +/- 0.2 pg/ml (mean +/- SEM). Neither the AVP-antagonist nor its vehicle had any effect on blood pressure, heart rate and skin blood flow as well as on plasma renin activity and plasma catecholamines. It is therefore concluded that circulating AVP does not contribute to the maintenance of blood pressure in patients with mild essential hypertension and normal plasma AVP levels.

Adult↗
PubMed1985

[Hemodynamic effects of an inhibitor of the vascular effects of vasopressin in patients with congestive heart failure].

To assess the role of vasopressin (AVP) in congestive heart failure (CHF), we investigated 10 patients with CHF refractory to conventional treatment, before and 60 minutes after intravenous administration of 5 micrograms/kg of d(CH2)5Tyr(Me)AVP, a specific antagonist of AVP at the vascular receptor level. Heart rate, systemic arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index by thermodilution, and cutaneous blood flow by laser-Doppler technique were measured. In 9 patients there was no significant hemodynamic and cutaneous blood flow response to the AVP antagonist. Plasma AVP was 2.3 +/- 0.8 pg/ml and plasma osmolality 284 +/- 14 mosm/kg H2O. The tenth patient had the most severe CHF. His plasma AVP was 55 pg/ml and plasma osmolality 290 mosm/kg. He responded to the AVP antagonist with a marked decrease in systemic arterial pressure from 115/61 to 79/41 mm Hg, in pulmonary arterial pressure from 58/31 to 33/13 mm Hg and in pulmonary capillary wedge pressure from 28 to 15 mm Hg. Simultaneously cardiac index increased from 1.1 to 2.21 X min-1 X m-2 and cutaneous blood flow rose 5-fold. Thus, most patients with CHF have only moderately elevated plasma AVP and its role in determining peripheral vascular resistance appears to be limited. AVP may become important in rare patients presenting with marked hemodynamic instability and very high plasma AVP.

Adult↗
PubMed1985

[Usefulness of ambulatory registration of arterial pressure in therapeutic trials of antihypertensive agents].

In the context of a controlled antihypertensive drug trial, blood pressure readings obtained by the physician in his office were compared with ambulatory blood pressures recorded with the semi-automatic Remler device. The beta-adrenoceptor blocking agent timolol or methyldopa were administered in double-blind fashion to 30 patients with uncomplicated essential hypertension. All exhibited a diastolic office blood pressure of greater than 95 mm Hg at the end of a 4-week placebo period. All patients then received a combination of hydrochlorothiazide (25 mg/d) and amiloride (2.5 mg/d). After 4 weeks of diuretic therapy, timolol (10 mg/d, n = 14) or methyldopa (250 mg/d, n = 16) were added randomly for 6 weeks. The dose of all antihypertensive agents was doubled after 2 weeks of therapy with diuretics combined with timolol (n = 7) or methyldopa (n = 16) because of the persistence of diastolic blood pressure levels of greater than 90 mm Hg at the office. When assessed in the office, the antihypertensive effect of timolol and methyldopa was similar. During ambulatory blood pressure monitoring, however, pressure levels tended to be lower in the patients given timolol (p less than 0.05 for the diastolic). These data show that ambulatory blood pressure monitoring may be very useful in comparing the antihypertensive efficacy of different drugs.

Adult↗
PubMed1985

Acute hemodynamic effect of a vascular antagonist of vasopressin in patients with congestive heart failure.

To assess the role of arginine vasopressin (AVP) in congestive heart failure (CHF), 10 patients with CHF refractory to conventional treatment were studied before and 60 minutes after intravenous administration of 5 micrograms/kg of d(CH2)5Tyr(Me)AVP, a specific antagonist of AVP at the vascular receptor level. Heart rate, systemic arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index by thermodilution and cutaneous blood flow by laser-Doppler technique were measured. In 9 patients with no significant hemodynamic and cutaneous blood flow response to the AVP antagonist, baseline values (mean +/- standard deviation) were: heart rate, 77 +/- 14 beats/min; systemic arterial pressure, 120/79 +/- 18/8 mm Hg; pulmonary arterial pressure, 42/21 +/- 12/8 mm Hg; pulmonary capillary wedge pressure, 19 +/- 7 mm Hg; cardiac index, 2.2 +/- 0.6 liters/min/m2; plasma AVP, 2.3 +/- 0.8 pg/ml; and plasma osmolality, 284 +/- 14 mosm/kg H2O. The tenth patient had the most severe CHF. His plasma AVP level was 55 pg/ml and plasma osmolality was 290 mosm/kg. He responded to the AVP antagonist with a decrease in systemic arterial pressure from 115/61 to 79/41 mm Hg, in pulmonary arterial pressure from 58/31 to 33/13 mm Hg and in pulmonary capillary wedge pressure from 28 to 15 mm Hg. Simultaneously, cardiac index increased from 1.1 to 2.2 liters/min/m2 and heart rate from 113 to 120 beats/min; cutaneous blood flow increased 5-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Transdermal clonidine therapy in hypertensive patients. Effects on office and ambulatory recorded blood pressure values.

The antihypertensive effect of clonidine hydrochloride delivered at a constant rate for seven days by transdermal disks was evaluated in seven patients with essential hypertension. Blood pressure values measured at the physician's office were not significantly decreased by one month of treatment with one (n = 2) or two (n = 5) once-weekly applied clonidine transdermal disks. In contrast, blood pressure values recorded during patients' customary daily activities by means of a portable blood pressure recorder were considerably reduced, from 159/97 +/- 2/2 to 136/76 +/- 7/5 mm Hg. Plasma drug concentration at the end of the fourth week averaged 1.22 +/- 0.24 ng/mL. Plasma renin, vasopressin, and epinephrine levels were not modified by clonidine, whereas plasma norepinephrine level was significantly reduced. Local skin erythema developed in three patients and dry mouth in six. These findings suggest that clonidine transdermal disks lower blood pressure in hypertensive patients, but produce local skin lesions and general side effects.

Administration, Topical↗
PubMed1985

Haemodynamic and pharmacological effects of the converting enzyme inhibitor CGS 14824A in normal volunteers.

The converting enzyme inhibitor CGS 14824A was evaluated in 15 healthy male volunteers. First, the efficacy of a single 5 or 10 mg oral dose in antagonizing the pressor response to exogenous angiotensin I was tested in 2 subjects. Blood pressure and heart rate were monitored continuously through an intra-arterial catheter. CGS 14824A 5 mg reduced the response to angiotensin I within 75 min to 50%, and 10 mg within 1 h to less than 25%, and for a period of more than 4 h. Subsequently, plasma renin and converting enzyme activity, plasma angiotensin I, angiotensin II and aldosterone were measured serially before and up to 72 h following oral administration of 2, 5, 10 or 20 mg CGS 14824A to groups of 5 volunteers. Plasma converting enzyme activity fell to well below 10% of baseline within 1 h after administration of 5 mg or more CGS 14824A. Within 2 h following 2 mg p.o., a similarly low level was reached. Twenty four hours following the 20 mg dose, plasma converting enzyme activity was still below 10%. As expected, plasma renin activity and angiotensin I rose while angiotensin II and aldosterone fell following the 2 mg dose. This pattern of effects was enhanced by increasing the dose. Nonetheless, 24 h after the 20 mg dose, plasma angiotensin II and aldosterone had returned to their baseline levels. No side-effects occurred. Thus, in normal volunteers, CGS 14824A was an effective, potent and long acting converting enzyme inhibitor.

Adult↗
PubMed1985

The effect of the converting enzyme inhibitor HOE 498 on the renin angiotensin system of normal volunteers.

The converting enzyme inhibitor HOE 498 was evaluated in 12 normotensive male volunteers aged 21 to 26. The efficacy of single 5, 10 or 20 mg oral doses in blocking the pressor response to exogenous angiotensin I was tested in 3 of the subjects. All 3 doses of HOE 498 reduced the pressor response to exogenous angiotensin I to below 50% of control within 1,5 h following administration of the drug. Plasma renin and converting enzyme activity, blood angiotensin I, as well as plasma angiotensin II and aldosterone were measured serially before and up to 72 h following oral administration of a single dose of 2.5, 5, 10 or 20 mg of HOE 498 to groups of 5 volunteers each. As expected, blood angiotensin I levels and plasma renin activity rose while plasma converting enzyme activity, plasma angiotensin II and aldosterone concentration fell after administration of the drug. While the dose of 2.5 mg did not reduce plasma converting enzyme activity below 20% of control, the higher doses all resulted in plasma converting enzyme inhibition exceeding 90%. No side-effects were observed. It is concluded that in normal volunteers HOE 498 is an effective potent and long-acting converting enzyme inhibitor. Based on these preliminary findings it is expected that 5 mg HOE 948 will turn out to be adequate for therapeutic use.

Administration, Oral↗
PubMed1985

Cardiac mass in glucocorticoid-hypertensive rats with and without circulating adrenaline.

There is evidence that catecholamines may promote the development of cardiac hypertrophy in hypertension. To test the hypothesis that adrenaline directly determines left ventricular mass, normotensive Wistar rats were made adrenaline-deficient by adrenalectomy and hypertensive by administration of glucocorticoid. Blood pressure, heart rate, and body weight of the adrenalectomised group were not significantly different from a glucocorticoid treated control group with intact adrenals. Heart weight was significantly lower in the adrenalectomised rats, but this difference disappeared when heart weight was adjusted for body weight. It appears therefore that the presence or absence of adrenaline does not significantly affect cardiac mass in the presence of hypertension in this animal model.

Adrenalectomy↗
PubMed1985

Blood pressure response to antihypertensive therapy: ambulatory versus office blood pressure readings.

Blood pressure readings obtained by the physician in his office and ambulatory blood pressures recorded with the semi-automatic Remler device, were compared during a controlled antihypertensive drug trial. Either timolol or methyldopa was administered in in double-blind fashion to 30 patients with uncomplicated essential hypertension. All exhibited a diastolic office blood pressure greater than 95 mmHg at the end of a four-week placebo period. All patients then received a combination of hydrochlorothiazide (25 mg/day) and amiloride (2.5 mg/day). After four weeks of diuretic therapy, timolol (10 mg/day, n = 14) or methyldopa (250 mg/day, n = 16) were added randomly for six weeks. The dose of all antihypertensive agents was doubled after two weeks of therapy with diuretics combined with timolol (n = 7) or methyldopa (n = 16) because of the persistence of diastolic blood pressure levels greater than 90 mmHg at the office. When assessed in the office, the antihypertensive effect of timolol and methyldopa was similar. During ambulatory blood pressure monitoring, however, pressure levels were lower in the patients given timolol (P less than 0.05 for the diastolic). With both regimens, the blood pressure response measured outside the clinic during usual daily activities could not be predicted from that observed with office blood pressure readings. Furthermore the magnitude of the drug induced blood pressure decrease was more reproducible in time when determined outside the clinic. These data suggest that ambulatory blood pressure monitoring is more precise in evaluating the efficacy of antihypertensive therapy than office blood pressure measurement.

Activities of Daily Living↗
PubMed1985

The present molecules of converting enzyme inhibitors.

Since the end of 1976 ten orally active converting enzyme inhibitors [SQ 14,225 (captopril), MK 421 (enalapril), MK 422, MK 521 (lysinopril), RHC 3659, CGS 13945, CGS 13928C, CGS 14824A, Hoe 498, S 9490-3, and Ro 31-2848] have been evaluated by our group in normal volunteers. Their ability to blunt the pressor response to exogenous angiotensin I and their effect on the different components of the renin-angiotensin system were tested. This approach has made it possible to establish the efficacy of the different molecules and to predict with a considerable degree of accuracy onset and duration of action of the various compounds as well as the doses needed to treat hypertensive patients. All ten molecules were effective in blocking converting enzyme and thereby the pressor response to angiotensin I. Potency and time course of the inhibition varied considerably among the compounds. Thus, a number of highly effective angiotensin-converting enzyme inhibitors are actually in clinical evaluation and several of them should become available for general clinical use within a few years.

Angiotensin II↗
PubMed1985

Effects of angiotensin converting enzyme inhibition: a clinical point of view.

Angiotensin converting enzyme inhibitors were developed to prevent the in vivo generation of angiotensin II and thereby to reduce peripheral vasoconstriction. However, these compounds exert some additional effects that may or may not be angiotensin dependent. These include potential sodium diuresis, bradykinin accumulation, prostaglandin release, blunting of sympathetic activity, parasympathomimetic actions, central effects, redistribution of blood flow toward some particularly important organs. Only the comprehensive assessment of the many complex interactions that exist between the renin-angiotensin and several other regulatory systems reveals the complete therapeutic profile of this class of pharmacologic agents.

Angiotensin I↗
PubMed1985

Angiotensin II, vasopressin, and sympathetic activity in conscious rats with endotoxemia.

The role of the sympathetic nervous system, angiotensin II (ANG II), and arginine vasopressin (AVP) in maintaining blood pressure (BP) during endotoxic shock was investigated in 117 conscious male Wistar rats. After intravenous injection of 2 mg Escherichia coli endotoxin, mean BP fell within 5 min by approximately 50 mmHg and rose again to approach base-line levels within 90 min. At that time, plasma renin activity, plasma norepinephrine (NE), and vasopressin levels of the endotoxin-treated animals were, respectively, 12-, 10-, and 54-fold (P less than 0.001) higher than those of the controls. The BP effect of either prazosin (0.125 mg iv), captopril (2.5 mg iv), or d(CH2)5Tyr(Me)AVP (5 micrograms iv), a specific antagonist of the vascular effect of AVP, was evaluated over a 30-min observation period starting 90 min after administration of endotoxin or its vehicle. Captopril reduced mean BP from 116 +/- 1.8 to a low of 109 +/- 2.1 (SE) mmHg (P less than 0.05, n = 8) only in rats pretreated with endotoxin, whereas the vasopressin antagonist had no depressor effect even during endotoxemia. The BP drop induced by prazosin in rats exposed to endotoxin (-21 +/- 3.3 mmHg, n = 6) did not significantly differ from that observed in control rats (-14 +/- 3.4 mmHg, n = 6). A dose-response curve to NE, ANG II, and lysine vasopressin was also performed. In endotoxin-treated rats the mean BP response to all agonists was markedly suppressed (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1985

Salt subtraction in patients on maintenance hemodialysis. Efficacy and limitations.

In 6 hypertensive patients with terminal renal failure maintained on hemodialysis, the effects of 'salt subtraction' and of sequential ultrafiltrating were evaluated. Following each of 3 weekly hemodialysis sessions, salt subtraction was carried out by ultrafiltrating 1 liter and simultaneously infusing an equal volume of 5% dextrose. This resulted in a net sodium loss without hypovolemia. After a 2-week period of this procedure, the blood pressure prior to dialysis was lower (156/76 +/- 12/5 mm Hg) than after a comparable number of sequential ultrafiltration sessions (181/88 +/- 10/6 mm Hg; mean +/- SEM). This difference was not statistically significant. At the same time, body weight was comparable at 64.4 +/- 3 and 64.7 +/- 4 kg, respectively. Neither plasma renin activity nor plasma catecholamines responded with a clear increase to either procedure. The limited effect on blood pressure and the renin system of a marked sodium removal during salt subtraction suggests that sodium must still be present in excess in these patients. The procedure of salt subtraction appears safe and subjectively well tolerated, but it can probably not be used as the sole means of decreasing total body sodium without associating dietary measures to reduce sodium intake.

Adult↗
PubMed1985

Shortcomings of office blood pressures in assessing antihypertensive therapy.

The antihypertensive effect of different agents was investigated in patients with essential hypertension both at the clinic and in the ambulatory state using the semi-automatic Remler M2000 blood pressure recorder. In 7 patients treated for 4 weeks with a transdermal therapeutic system delivering clonidine, blood pressures measured at the physician's office were not significantly decreased whereas blood pressures recorded during patients' customary daily activities were markedly reduced. In an additional study performed in double-blind fashion, the blood pressure lowering effect of timolol (10-20 mg/d, n = 14) and of methyldopa (250-500 mg/d, n = 16) were compared. These agents were given for 6 weeks in association with a baseline diuretic therapy of hydrochlorothiazide and amiloride. When assessed at the clinic, the antihypertensive effect of timolol and methyldopa was similar. During ambulatory blood pressure monitoring, however, pressure levels were lower (p less than 0.05 for the diastolic) in the patients given timolol. These data indicate that blood pressure monitoring outside the clinic makes it possible to detect important differences in the response to antihypertensive therapy even though, based on office blood pressure readings, no significant change occurs. It appears therefore desirable to include ambulatory blood pressure recordings in the design of drug trials.

Antihypertensive Agents↗