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Biomedical subjects

H R Brunner

Publications and source records attributed to H R Brunner.

At least 559 records · Page 31Linked to original sources
PubMedDate not supplied

Dose-dependent effect of atrial natriuretic peptide on blood pressure, heart rate, and skin blood flow of normal volunteers.

Synthetic atrial natriuretic peptide, containing 26 amino acids in the rat sequence, L-364, 343 (Ileu-ANP), was infused intravenously at increasing rates (1-40 micrograms/min) into four normal volunteers. Mean intraarterial blood pressure decreased and heart rate increased in cumulative-dose-dependent fashion. Skin blood flow as measured with a laser Doppler device rose already with a cumulative dose of 55 micrograms Ileu-ANP and further rises were directly related to dose. The only side effects observed were those accompanying symptomatic hypotension at higher doses. These findings provide strong evidence that Ileu-ANP acts as a vasodilator in normal volunteers.

Adult↗
PubMedDate not supplied

Unpredictability of blood pressures recorded outside the clinic in the treated hypertensive patient.

Ambulatory blood pressure profiles were obtained with the Remler M2000, a portable semiautomatic blood pressure recorder, in 38 chronically treated hypertensive patients who continued to have blood pressures measured by their physician greater than 140 mm Hg systolic and greater than 89 mm Hg diastolic. On the average, ambulatory recorded blood pressures were significantly lower (151/94 +/- 26/13 mm Hg; mean +/- SD) than those determined at the clinic not only by a physician (179/109 +/- 22/11 mm Hg), but by a nurse (163/101 +/- 24/10 mm Hg). Individual mean recorded ambulatory blood pressures could be predicted neither from office readings obtained by a physician nor from those measured by a nurse. Because of this unpredictability of blood pressures prevailing outside the clinic, ambulatory blood pressure monitoring seems to be very useful, if not necessary, in assessing the efficacy of antihypertensive drugs. By this technique, it may be possible to select patients who do not need a change of treatment although their blood pressure levels remain persistently elevated in the physician's office.

Blood Pressure Determination↗
PubMedDate not supplied

Intraluminal pressure modulates the magnitude and the frequency of induced vasomotion in rat arteries.

Arterial vasomotion and its relation to intraluminal pressure were investigated in vitro in isolated rat arteries. Femoral arteries (mean diameter = 768.2 +/- 25 microns, n = 5) and mesenteric arteries (mean diameter = 393.4 +/- 32 microns, n = 5) were used in this study. Arterial segments were excised, mounted on microcannulas and perfused with Tyrode's solution at a constant flow (100 microliters/min). After equilibration, intraluminal pressure was stepwise changed from 0 to 120 mm Hg. The changes in the outer diameter of the vessels were measured continuously over a period of 4 h after the equilibration. Vasomotion was induced by constrictor agonists (norepinephrine 10(-6) M for mesenteric arteries and norepinephrine 10(-6) M + Bay K8644 10(-7) M for femoral arteries) and was maintained only in the presence of the above-mentioned drugs. Both vasomotion magnitude and frequency are modulated by pressure. Vasomotion frequency increases with pressure increase. When intraluminal pressure varied between 0 and 120 mm Hg, vasomotion frequency varied between 0.19 and 0.49 Hz for mesenteric arteries and between 0.04 and 0.23 Hz for femoral arteries. Thus, vasomotion frequency differed clearly between the two vessel types. Vasomotion amplitude shows a biphasic relationship with a maximum occurring at about 40 mm Hg for mesenteric arteries and 50 mm Hg for femoral arteries. Based on these findings, it is hypothesized that vasomotion amplitude relates to the active mechanical properties of the artery and, in particular, to its contractile capacity.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMedDate not supplied

Discrepancy between antihypertensive effect and angiotensin converting enzyme inhibition by captopril.

Captopril, an inhibitor of angiotensin converting enzyme, was administered twice daily to 13 hypertensive patients for a mean period of 9 weeks. Continuous blood pressure control in the ambulatory patients was established with a portable blood pressure recorder. Notwithstanding, in eight patients with normal renal function, plasma converting enzyme was found to resume normal activity before administration of the morning dose of captopril. Only in 5 patients with impaired renal function did some blockade of plasma converting enzyme persist for more than 12 hours. Measured plasma converting enzyme activity seemed to reflect total conversion of angiotensin I, including conversion in the pulmonary vascular bed, since changes in its activity were closely paralled by changes in plasma aldosterone levels. Bradykinin accumulation seems unlikely when converting enzyme and thus, presumably, kininase II has resumed normal activity. Captopril administration does not seem to alter plasma epinephrine or norepinephrine levels. Blood pressure reduction in the face of normal angiotensin converting enzyme activity is probably due to hyporesponsiveness of the arterioles to pressor hormones, which may be due to specific renin-related and/or nonspecific effects of captopril.

Adult↗
PubMedDate not supplied

Converting enzyme inhibition during chronic angiotensin II infusion in rats. Evidence against a nonangiotensin mechanism.

Interpretation of results obtained with angiotensin-converting enzyme inhibition in hypertensive patients has been obscured by the possibility of nonangiotensin-mediated mechanisms, particularly rats, we have compared the effects of converting enzyme inhibition (CEI) by oral captopril administration to those of dextrose. In this setting of constant angiotensin II levels, any apparent effects of CEI must be mediated by a nonangiotensin-related mechanism. Angiotensin II infusion at 30 ng/min increased mean blood pressure by an average of 22 mm Hg. Following 7 days of CEI, effective blockade of converting enzyme was established both by a 10-fold elevation of vasodepressor sensitivity to exogenous bradykinin and a markedly decreased plasma converting enzyme activity. On the ninth day of angiotensin II infusion, mean arterial pressure, heart rate, and plasma renin activity were not different between CEI and dextrose-treated groups. Similarly, blockade of angiotensin II by saralasin induced a comparable fall in blood pressure in both groups. Metabolic studies also revealed no long-term differences in water and food intake, weight change, or sodium and potassium metabolisms. These findings suggest that, in the continued presence of angiotensin II, there is no detectable hemodynamic or metabolic effect of chronic converting enzyme inhibition, and therefore that bradykinin plays little or no role in its long-term antihypertensive action.

Angiotensin II↗
PubMedDate not supplied

Norepinephrine and renin activity in chronic renal failure. Evidence for interacting roles in hemodialysis hypertension.

To assess the interaction between adrenergic activity and blood pressure regulation in patients with chronic renal failure, plasma norepinephrine (NE) and plasma renin activity (PRA) were measured before and after vigorous ultrafiltration. The significance of PRA was further assessed by angiotensin blockade with saralasin. Two patterns of response were defined: nine patients had low levels of PRA before and after hemodialysis. These patients showed a net fall in norepinephrine and no angiotensin dependence of any time. Failure to stimulate either PRA or norepinephrine was also observed during periods of marked hypotension. Seven other patients had higher PRA, which rose during hemodialysis. This was associated with an increase in NE and postdialysis angiotensin dependence. Patients experiencing hypotension in this group showed a sharp rise in NE, suggesting baroceptor-mediated adrenergic stimulation. In all patients sustaining hypotension during therapy, postdialysis PRA was closely correlated with NE. These results indicate that hemodialysis mobilizes the renin-angiotensin system to maintain hypertension in a greater proportion of dialysis patients than previously supposed and that impaired renin release following hypotension may represent uremic autonomic dysfunction.

Adult↗
PubMedDate not supplied

Role of reactive hyperreninemia in blood pressure changes induced by sodium depletion in patients with refractory hypertension.

Sixteen patients with refractory hypertension were submitted to vigorous sodium depletion while cardiovascular homeostasis was monitored with measurements of hormonal and hemodynamic parameters and repeat saralasin tests. This regimen resulted in a negative sodium balance by an average of 300 mEq. The loss of sodium closely correlated to the decrease of body weight (r = 0.70, p less than 0.005). Blood pressure (BP) decreased from 176/166 +/- 8/3 to 155/109 +/-6/3 mm Hg. There was a significant correlation between percent increments in plasma renin activity (PRA) and the rise in plasma norepinephrine (r = 0.68, p less than 0.05) and a close negative correlation between percent increase in PRA and the ratio of fall in mean blood pressure (MAP) per unit of weight loss (r = -0.73, p less than 0.005). Thus, patients with the least percent increase in PRA demonstrated the greatest fall in BP per unit of weight loss, indicating that relative rather than absolute elevation of renin may be the factor limiting antihypertensive efficacy of sodium depletion. Sodium depletion induced increase in peripheral resistance and decrease in cardiac output, both mostly attributable to relative hyperreninemia. Indeed, the adverse hemodynamic changes were reversed by angiotensin inhibition, during which BP normalized. It is concluded that vigorous sodium depletion complemented by angiotensin blockade or suppression with sympatholytic agents improves management of otherwise refractory hypertension.

Adult↗
PubMedDate not supplied

Does pharmacological profiling of a new drug in normotensive volunteers provide a useful guideline to antihypertensive therapy?

Similar pressor mechanisms should be active in hypertensive and normotensive subjects since hypertension is a quantitative rather than qualitative disorder. Consequently, if an antihypertensive drug is designed to specifically block a well-defined mechanism involved in blood pressure regulation, it should be possible to evaluate its efficacy rather precisely in normotensive volunteers before even administering the compound to a hypertensive patient. That this is indeed the case is illustrated by the example of angiotensin-converting-enzyme inhibitors. The magnitude of blockade that can be obtained in humans, the minimal does needed for maximal efficacy, and the onset and duration of action of the agents have all been precisely determined in normotensive volunteers. Subsequent administration to hypertensive patients merely confirmed these findings. Moreover, if the antihypertensive effect of converting-enzyme inhibitors could not be predicted in an individual hypertensive patient, this is not related to some unknown action of the drug that cannot be assessed in normal volunteers but rather to our lack of understanding of the precise mixture of pathogenetic mechanisms prevailing in any particular patient. Only the safety evaluation and the search for side-effects still has to be carried out in nonspecific fashion, thus requiring long-term observations in large numbers of patients. If the tolerance of new converting-enzyme inhibitors were more predictable, the number of studies in hypertensive patients could be drastically reduced since the antihypertensive profile of any new converting-enzyme inhibitor can probably be precisely determined in normotensive volunteers.

Aldosterone↗
PubMedDate not supplied

Does renin determine the blood pressure response to calcium entry blockers?

Male Wistar rats with one-kidney, one clip renal hypertension were maintained on either a regular or a low salt diet for 3 weeks after clipping. At that time mean blood pressure in the unanesthetized rats was equally elevated in sodium-depleted (n = 17) and in sodium-replete rats (n = 19), but plasma renin activity was significantly higher in the former (p less than 0.05). Infusion of the calcium entry blocker verapamil at a rate of 0.05 mg/kg/minute decreased blood pressure within 60 minutes to a similar extent in rats kept on a salt-deficient diet and in rats fed a regular salt diet. In all rats taken as a group, there was a close, direct correlation (r = 0.87, p less than 0.001) between the magnitude of the blood pressure response to verapamil and the pretreatment blood pressure levels. Verapamil markedly accelerated heart rate and stimulated renin release in all rats. In additional groups of sodium-depleted (n = 8) and sodium-replete renal hypertensive rats (n = 7), nifedipine administration (4 micrograms/kg/min i.v.) within a 45-minute observation period caused a blood pressure fall (p less than 0.001) and heart rate acceleration (p less than 0.001) that were comparable in both groups. These findings suggest that in the rat with renal hypertension the short-term blood pressure response to the calcium antagonists verapamil and nifedipine is not influenced by the state of sodium balance and plasma renin activity. In this experimental model of hypertension, the magnitude of the blood pressure lowering effect of calcium entry blockers appears to be proportional to pretreatment blood pressure levels.

Animals↗
PubMedDate not supplied

True versus immunoreactive angiotensin II in human plasma.

To measure specifically angiotensin-(1-8)octapeptide, peptides were extracted from 2 ml of plasma by reversible adsorption to bonded-phase silica. The angiotensin-(1-8)octapeptide was then isolated by isocratic reversed-phase high-performance liquid chromatography and quantified by radioimmunoassay. The extraction recovery of 125I-angiotensin II added to 2 ml of plasma was 99 +/- 2% (mean +/- SD). The overall recovery of 5, 10, and 20 fmol unlabeled angiotensin II added to 1 ml of plasma was 80 +/- 10%. The coefficient of variation for within-assay precision was 0.06 and for between-assay precision 0.13. The detection limit was 0.4 fmol/ml. Buffer and plasma blanks were below the detection limit. Normal subjects on a free diet in supine position averaged 4.2 +/- 1.7 fmol/ml angiotensin-(1-8)octapeptide. Furosemide (40 mg p.o.) and standing increased these values to 22 +/- 7.6 fmol/ml. In four volunteers, immunoreactive "angiotensin II" (more or less angiotensin-like material) was measured serially before and after converting-enzyme inhibition (Hoe 498) with conventional Dowex extraction. At peak inhibition, plasma immunoreactive "angiotensin II" levels decreased by only 44%. In contrast, angiotensin-(1-8)-octapeptide isolated by high-performance liquid chromatography completely disappeared. In hypertensive patients receiving long-term treatment with enalapril, plasma levels of angiotensin-(1-8)octapeptide fell from 2.7 +/- 0.9 to 0.9 +/- 0.3 fmol/ml (mean +/- SEM) 2 hours after the morning dose, whereas levels of immunoreactive "angiotensin II" were not significantly changed. We found that this sensitive method specifically measured angiotensin-(1-8)octapeptide and demonstrated that true angiotensin II virtually disappears during converting-enzyme inhibition.

Adult↗
PubMedDate not supplied

Individual measurements of angiotensin II concentrations in aqueous humor of the eye.

The presence of constituents of the renin-angiotensin system (RAS) in ocular tissues and fluids suggests this system is involved in ocular physiology. Angiotensin II (AngII) is the main biological effector of the system, so we measured AngII in plasma and in aqueous humor of the anterior ocular chamber of patients undergoing cataract extraction. Untreated normotensive patients were compared with arterial hypertensive patients taking either diuretics which stimulate the RAS or angiotensin converting enzyme (ACE) inhibitors which reduce the production of AngII. Plasma levels of AngII were higher in patients on diuretics (5.46 +/- 1.04 fmol/ml; mean +/- SEM) than in untreated cataract patients (2.28 +/- 0.32 fmol/ml, p < 0.02), and were very low with ACE inhibitors (0.51 +/- 0.18 fmol/ml). In aqueous humor, AngII was measurable in 7 of 11 patients on diuretics (median 1.1 fmol/ml), and in 6 of 16 normotensive patients (median < 0.55 fmol/ml), but not in aqueous humor of 4 patients receiving enalapril or captopril. These results demonstrate the presence of AngII in the eye but do not exclude either its sequestration in the eye or local production. The possibility of individual measurements of intraocular AngII will permit more precise determination of its role in future studies.

Aged↗
PubMedDate not supplied

Compliance with antihypertensive therapy.

Poor compliance with antihypertensive therapy is a major cause of unsatisfactory blood pressure control. The doctor has a key role in all steps that lead the patient to adopt a treatment and to take it as prescribed lifelong. Compliance with therapy is a parameter which is difficult to assess. There is often an important mismatch between the subjective views of physicians and patients regarding long-term drug taking. Electronic monitoring of compliance represents a valuable method to evaluate the "real time" compliance of the patient. Discussing a compliance recording with a patient may help to identify and solve problems linked with everyday adherence to antihypertensive treatment. Improving compliance is an important task not only for the doctors, but also for all healthcare providers.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Improved blood pressure control by monitoring compliance with antihypertensive therapy.

Compliance with antihypertensive therapy was monitored for three months using an electronic medication dispenser in 35 patients remaining hypertensive despite the once-daily administration of a blood pressure lowering drug (either as monotherapy or as fixed-dose combination therapy). During the monitoring of compliance, the treatment was unchanged but blood pressure decreased significantly (p < 0.001) from 167.9/100.4 +/- 16.3/7.2 mmHg (mean +/- SD) to 152.5/90.9 +/- 20.9/11.5 mmHg. The percentage of days with one opening per day was 80.8 +/- 20.5. Thus, discussing with the patient about compliance with the prescribed drug regimen and monitoring compliance for a few months allows better control of blood pressure. This most likely reflects increased compliance with antihypertensive drug therapy.

Adult↗
PubMedDate not supplied

Antihypertensive therapy with MK 421: angiotensin II--renin relationships to evaluate efficacy of converting enzyme blockade.

Nineteen hypertensive patients were treated with increasing doses of the new angiotensin-converting enzyme inhibitor MK 421. Twenty milligrams orally reduced blood pressure from 180/112 +/- 6.8/3.6 (mean +/- SEM) to 160/100 +/- 6.5/3.3 mm Hg (p less than 0.005) while heart rate increased from 75 +/- 2 to 87 +/- 3 beats/min (p less than 0.005). Plasma converting enzyme activity was still markedly reduced 24 h following 2.5, 5, 10, or 20 mg MK 421 p.o. (p less than 0.001). In nine patients treated with 20 mg b.i.d. for up to 10 months, blood pressure was controlled, with the association of hydrochlorothiazide 50 mg q.d. in five. However, 12 to 16 h following the preceding drug administration, plasma angiotensin II and aldosterone were back to base-line levels. Analysis of plasma angiotensin II-renin relationships strongly suggests that converting enzyme blockade is not complete even 4 h after 20 mg MK 421 and starts to wear off already at 12 h. Thus, MK 421 20 mg taken orally twice daily, effectively reduces blood pressure, but does not constantly suppress plasma angiotensin II and aldosterone. Whether its long duration of action makes once daily administration possible has not yet been established.

Adult↗
PubMedDate not supplied

CGS 13945: a new orally active angiotensin-converting enzyme inhibitor in normal volunteers.

The new converting enzyme inhibitor CGS 13945 was evaluated in 14 male volunteers. The study consisted of two parts. First, the capacity of a single oral dose (10, 20, 50, 100, 250, or 500 mg) to inhibit the pressor response to exogenous angiotensin I was tested, with blood pressure and heart rate monitored continuously through an intra-arterial catheter. The 250-mg and particularly the 500-mg dose markedly reduced the pressor response to angiotensin I within 1/2 h and for a period exceeding 4 h. There was a close correlation between the pressor response to angiotensin I and plasma converting enzyme activity. In a second part, plasma renin and converting enzyme activity, angiotensin I and II, and plasma aldosterone were measured serially before and up to 48 h after oral administration of either 250 or 500 mg of CGS 13945 to six volunteers each. As expected, plasma renin activity and angiotensin I levels rose, while plasma converting enzyme activity and angiotensin II and aldosterone levels fell within 1/2 h. Twenty-four hours following administration of 500 mg CGS 13945, plasma converting enzyme had not quite returned to base line. No side effects were observed. CGS 13945 seems less potent than previously studied converting enzyme inhibitors, but equally effective and relatively long acting.

Adult↗