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Biomedical subjects

H R Brunner

Publications and source records attributed to H R Brunner.

At least 541 records · Page 30Linked to original sources
PubMed1972

Angiotensin II vascular receptors: their avidity in relationship to sodium balance, the autonomic nervous system, and hypertension.

During intravenous administration of varying doses of angiotensin II antibody to anesthetized rats, apparently specific vascular receptors were characterized. These receptors compete with administered antibody to bind circulating angiotensin. This competitive phenomenon was used to evaluate the affinity of these receptors for angiotensin. Apparent vascular receptor affinity was defined by the amount of antibody required to block the blood pressure response to exogenous angiotensin. It was found that this receptor affinity varies directly with sodium intake so that the amount of antibody required to block was eightfold greater in normal animals on a high sodium intake, as compared with those on a low sodium intake. Sodium dependence of receptors was also demonstrated in nephrectomized animals, in desoxycorticosterone (DOC)-treated rats, and in chronic renal hypertension. Thus the observed changes in receptor affinity were usually inversely related to measured endogenous angiotensin II levels. Ganglionic blockade increased antibody requirement eightfold. All of these changes were consistent, with no overlap observed in response of individual animals from different groups. These results may explain the variation in pressor activity of angiotensin associated with changes in salt balance and ganglionic blockade. In general, when sufficient antibody was injected to block the effect of exogenous angiotensin a blood pressure lowering effect was also observed. Two exceptions were the nephrectomized and the one-kidney renal hypertensive animals, in both of which antibody administration had no effect on blood pressure. Additional results suggest that changes in receptor affinity are involved in the pathogenesis of various types of experimental hypertensions because the amount of antibody required to block angiotensin was enhanced in renal (twofold), DOC (fourfold), and genetic (fourfold) hypertension. Accordingly, changes in the affinity of these receptors could be critically involved in normal blood pressure control and in various forms of experimental and clinical hypertension, even when circulating angiotensin II levels are normal.

Angiotensin II↗
PubMed1971

Hypertension of renal origin: evidence for two different mechanisms.

Antibody to angiotensin 11, or a specific peptide competitive inhibitor of angiolensin II, was used to investigate the role of the renin-angiotensin system in two types of renal hypertension in rats. The data indicate that angiotensin II is in fact critically involved in the pathogenesis of the form of renal hypertension in which one renal artery is clamped and the contralateral kidney is left in place, but that it probably plays no significant role in the maintenance of experimental renal hypertension in which the opposite kidney has been removed.

Angiotensin II↗
PubMed1970

The influence of potassium administration and of potassium deprivation on plasma renin in normal and hypertensive subjects.

The effect of potassium administration and of dietary potassium deprivation on plasma renin activity and aldosterone excretion has been studied in 10 normal subjects and in 12 hypertensive patients maintained on a constant dietary regimen. Potassium administration reduced plasma renin activity in 18 of 28 studies of both normal and hypertensive subjects. Suppression of renin often occurred despite sodium diuresis induced by potassium administration. The renin suppression was related to induced changes in plasma potassium concentration and urinary potassium excretion. The failure of suppression of plasma renin in 10 studies could be accounted for by the smaller amounts of potassium administered to these subjects, together with a possibly overriding influence of an induced sodium diuresis. In six studies potassium deprivation invariably increased plasma renin activity even though a tendency for sodium retention often accompanied this procedure. The data indicate that both the suppression of plasma renin activity induced by potassium administration and the stimulation of renin activity which follows potassium depletion occur independently of associated changes in either aldosterone secretion or in sodium balance. However, the results do suggest that in various situations, the influence of potassium on plasma renin activity may be either amplified or preempted by changes in sodium balance. These interactions between potassium and plasma renin could be mediated by an ill-defined extrarenal pathway. But the findings are more consistent with an intrarenal action of potassium ions to modify renin release. Potassium might modify renin secretion directly by acting on the juxtaglomerular cells or by a change in its tubular reabsorption or secretion. The effects of potassium ions on renin secretion might also be mediated indirectly via an induced change in tubular sodium transport.

Adult↗
PubMedDate not supplied

Effect of a new beta-adrenergic blocker, l-bunolol, on blood pressure and on the renin-aldosterone system.

The antihypertensive effect of a new beta-adrenergic receptor blocker, l-bunolol, was evaluated in 11 hospitalized hypertensive patients of whom four belonged to the high-renin, five to the normal-renin, and two to the low-renin subgroup. There was a significant decrease in blood pressure in most patients, often to normal. Moreover, plasma renin levels were nearly always markedly suppressed, and this suppression preceded the fall in blood pressure. While most high and normal renin patients responded, the numbers of patients within each subgroup were too small to correlate the blood pressure responses with changes in renin levels. There was a significant induced decrease in aldosterone excretion, which usually paralleled the renin suppression. Pulse rate was also consistently reduced during treatment. No weight gain was observed, except in one patient who developed overt congestive cardiac failure. No other side effects were recorded. Ii is concluded that l-bunolol is another beta-blocking drug with significant antihypertensive action. It was found to be effective in cases that were resistant to propranolo. It is well tolerated and safe to use, provided that early evidence of fluid retention is sought for and treated immediately.

Adult↗
PubMedDate not supplied

Effect of nadolol in treatment of hypertension.

Nadolol, a new beta-adrenergic blocking agent, was administered orally in gradually increasing single daily doses to 13 hospitalized patients with essential hypertension. Maximal doses ranged from 200 to 480 mg/day. Blood pressure was reduced in nine patients and heart rate was decreased in 11 patients. The decrease in blood pressure was either partial or temporary in five of the nine patients who responded. Concomitant administration of the diuretic chlorthalidone decreased blood pressure in a previously unresponsive patient. Nadolol effectively inhibited isoproterenol-induced tachycardia and decreased cardiac output by 18 per cent. Plasma renin activity and plasma aldosterone concentration were not changed significantly by the treatment. Body weight was not altered significantly. Blood pressure response was independent of the pretreatment renin levels or the change in renin induced by nadolol; it was also independent of the changes in cardiac output and heart rate but was more pronounced in patients with milder baseline hypertension. The decline in serum concentration of nadolol was consistent with the drug's reported half-life of 12.2 hours. The results indicate that single daily doses of nadolol alone can reduce blood pressure significantly with minimal cardiodepressant effects and no important side effects. The effectiveness of nadolol may be enhanced by the addition of a diuretic.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Safety and efficacy of chronic therapy with captopril in hypertensive patients: an update.

Captopril, an orally active angiotensin-converting enzyme inhibitor, has been administered to 81 patients with different types of clinical hypertension. Most of the patients had previously uncontrollable high blood pressure. In order to achieve a satisfactory blood pressure control during long-term captopril therapy, a concomitant decrease in total body sodium was required in more than half of the patients. During our first two years of clinical experience with this new antihypertensive agent, side effects developed in 46.9 per cent of the patients and necessitated the withdrawal of the drug in 23.4 per cent of all patients. Only a few side effects such as hypotensive or syncopal episodes and cold extremities appeared to be due to the chronic blockade of the renin-angiotensin system. The most frequent and the most serious adverse reactions such as skin rash, altered taste, pancytopenia, and pemphigus foliaceus seemed to be specifically drug related. The incidence of cutaneous and taste problems was markedly higher in patients with impaired renal function in whom retention of captopril has been previously demonstrated. This suggests that the occurrence of adverse reactions to captopril could be lowered in the future by using smaller daily doses and by titrating them according to the renal function.

Adolescent↗
PubMedDate not supplied

A device for subjecting vascular endothelial cells to both fluid shear stress and circumferential cyclic stretch.

The proposal of the role of mechanical forces as a localizing factor of atherosclerosis has led many researchers to investigate their effects on vascular endothelial cells. Most previous efforts have concentrated on either the fluid shear stress, which results from the flow of blood, or the circumferential "hoop" stretch, which results from the expansion of the artery during the cardiac cycle. In fact, arterial endothelial cells are subjected to both fluid shear stress and cyclic hoop stretch in vivo. Therefore, a more complete investigation of mechanical phenomena on endothelial cell behavior should include both kinds of mechanical stimuli. This study was undertaken to design an experimental apparatus that could subject cultured vascular endothelial cells to simultaneous physiologic levels of both shear stress and cyclic hoop stretch. The experimental apparatus consists of four cylindrical elastic tubes so that the following conditions may be studied: (a) static conditions: (b) shear stress only; (c) hoop stretch only; and (d) shear stress and hoop stretch. In order to establish the functional capabilities of the apparatus, bovine pulmonary artery endothelial cells were cultured in the tubes, and their morphology and f-actin structure were observed with confocal microscopy. The cells remained healthy and attached to the walls throughout the 24 hr experiment. Preliminary results indicated that the alignment of endothelial cells subjected to shear stress was significantly enhanced by the addition of hoop strain.

Actins↗
PubMedDate not supplied

A sensitive and specific two-site, sandwich-amplified enzyme immunoassay for neuropeptide Y.

The development of a new enzyme immunoassay for neuropeptide Y (NPY) is reported. Two monoclonal antibodies directed against distinct epitopes of NPY are used, one as a capture antibody (NPY02) and the other one as an indicator antibody (NPY05), this latter antibody being labeled with alkaline phosphatase. The assay calibration curve was performed over concentrations of 1 to 250 pM in a NPY-free plasma. The intra-assay coefficient of variation (CV) ranged from 0.025 to 11.9%, whereas the interassay CV was comprised between 5 and 12%. The limit of detection of this assay was 1 pM (100 amol/well). Neuropeptide Y levels are related to sampling conditions; basal concentrations of NPY with low SEM are found when less than 1.2 ml of blood is taken in EDTA tubes, the sample is centrifuged at 4 degrees C, and immediately frozen. Unanesthetized spontaneously hypertensive rats exhibited higher NPY plasma concentrations than normotensive Wistar-Kyoto controls (53 +/- 7 pM and 25 +/- 2 pM, respectively, mean +/- SEM, p < 0.01). Plasma NPY levels are similar in 16- and 36-week-old animals. In conclusion, this technique makes it possible to assay a large number of samples within 24 h without requiring radioactivity.

Amino Acid Sequence↗
PubMedDate not supplied

Salt- and angiotensin II-dependent variations in amiloride-sensitive rectal potential difference in mice.

1. In the rectum and distal nephron, sodium reabsorption is mediated by the amiloride-sensitive epithelial sodium channel (ENaC). The ENaC-mediated sodium transport is electrogenic and creates an amiloride-sensitive transepithelial potential difference (PD). 2. We have evaluated the salt- and angiotensin (Ang)II-dependent variations in amiloride-sensitive rectal PD in mice and assessed their relationship with renal sodium handling. 3. Rectal PD was measured in vivo in mice maintained on a medium-, low- or high-sodium diet. On a medium-salt diet, the mean (+/- SEM) amiloride-sensitive PD was larger in the afternoon than in the morning (-26.1 +/- 0.9 and -11.2 +/- 0.7 mV, respectively; P = 0.001), indicating a circadian cyclicity. Rectal PD increased on a low-sodium diet and decreased on a high-sodium diet. 4. Amiloride-sensitive rectal PD correlated significantly with the urinary Na+/K+ ratio (P < 0.001) and with sodium reabsorption in the distal nephron as measured by the lithium clearance technique (P < 0.001). 5. In mice treated with an AngII AT1 receptor antagonist, amiloride-sensitive rectal PD was increased in the afternoon compared with controls (-32.8 +/- 2.0 vs -24.4 +/- 0.9, respectively; P < 0.001). 6. At high doses, AngII decreased the amiloride-sensitive rectal PD and this effect was blunted by an AT1 receptor antagonist. 7. These results show the presence of a salt-dependent daily cyclicity of sodium transport in the mouse rectum that follows circadian changes in sodium handling in the distal nephron. Angiotensin II appears to modulate this diurnal pattern of rectal amiloride-sensitive sodium transport.

Angiotensin II↗
PubMedDate not supplied

Pre- and postsynaptic effects of SKF64139, a phenylethanolamine N-methyltransferase inhibitor, in conscious normotensive rats.

We investigated in conscious normotensive rats the effect of SKF64139 (2 mg i.v.), a potent phenylethanolamine N-methyltransferase (PNMT) inhibitor, on blood pressure responses to norepinephrine (40, 80, and 160 ng i.v.); methoxamine (2.5, 5 and 10 micrograms i.v.), a directly active sympathomimetic agent that is not taken up by adrenergic nerves; and tyramine (20, 40, and 80 micrograms i.v.), an indirectly acting sympathomimetic amine. The pressor effect of norepinephrine was not changed by 2 mg of SKF64139, while those of methoxamine and tyramine were significantly reduced. The dose-response curve to exogenous norepinephrine was also evaluated following blockade of norepinephrine uptake in the nerve endings using 0.25 mg desipramine i.v. This dose of desipramine had no effect on blood pressure increase induced by methoxamine. In rats pretreated with the neuronal uptake inhibitor desipramine in a dose that did not affect alpha-adrenoceptors, SKF64139 significantly decreased the pressor responses to norepinephrine. Increasing the dose of SKF64139 to 8 mg i.v. resulted in a significant fall in base-line blood pressure and in a blunted blood pressure response to norepinephrine. These data demonstrate that in vivo the PNMT inhibitor SKF64139 blocks alpha-adrenoceptors and inhibits neuronal uptake. The alpha-adrenoceptor blocking properties of SKF65139 are masked by simultaneous blockade of norepinephrine uptake when agonists with affinity for the uptake system are used. These findings need to be taken into account when interpreting cardiovascular effects of the PNMT inhibitor SKF64139.

Animals↗
PubMedDate not supplied

Blood pressure variability in ambulatory hypertensive patients: effect of beta-blocking agents and/or diuretics.

Using a semiautomatic device (Remler), ambulatory blood pressure was recorded in ambulatory hypertensive patients who were either untreated (n = 55) or treated chronically with beta-blocking agents (n = 28), diuretics (n = 42), or a combination of both (n = 75). In all patients, one blood pressure reading was obtained during usual activities every 30 min for 12 h. The selection of untreated patients was based on clinic measurements (two to three repeated blood pressures of greater than 140/89 mm Hg). The mean systolic and diastolic blood pressures averaged from all patients over the whole day did not differ significantly among the groups, ranging from 133.7 to 141 mm Hg for the systolic and from 83.8 to 88.4 mm Hg for the diastolic. The variability of blood pressure, reflected by the difference between the average of the three highest and the three lowest values of the day, was not different among the four groups and ranged from 41.4 to 50.6 mm Hg for the systolic and from 30.1 to 34.4 mm Hg for the diastolic. Similarly, variability expressed as the standard deviation of the mean of all blood pressures measured during the day did not differ among the groups. In all groups, blood pressure was highest in the morning and lowest in early afternoon, and tended to rise again in the late afternoon. Thus, blood pressure variability of hypertensive patients is not changed by antihypertensive therapy with beta-blocking agents and/or diuretics.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Enhanced acute antihypertensive effect of propranolol in the absence of circulating epinephrine in the rat.

beta-Adrenoceptor blocking agents might reduce blood pressure, in part, by blocking presynaptic beta-adrenoceptors. Absence of circulating epinephrine should then reduce the antihypertensive effect of propranolol. Biadrenalectomized Wistar-Kyoto rats were made hypertensive with methylprednisolone (20 mg/kg s.c. weekly), given for 2 weeks, and supplemented with deoxycorticosterone pivalate (10 mg/kg weekly). Sham-operated controls received the same treatment. Baseline weight, mean intraarterial blood pressure, and heart rate of the groups were the same. After propranolol (5 mg/kg s.c.) was administered to the unanesthetized rats, blood pressure fell within 90 min from 151 +/- 4 by 23 +/- 4 mm Hg (mean +/- SEM) in the adrenalectomized animals and from 153 +/- 4 by only 7 +/- 3 mm Hg in the sham-operated controls (p less than 0.001); heart rate fell by 91 +/- 13 beats/min in the adrenalectomized animals and by 40 +/- 11 beats/min in the controls (p less than 0.01). Propranolol's vehicle had no effect. At the end of the experiment, plasma epinephrine levels were less than 40 pg/ml for adrenalectomized rats, and 420 +/- 60 pg/ml for controls. Norepinephrine levels were approximately equal in the two groups. Since blood pressure fell despite virtual absence of circulating epinephrine, these results suggest that propranolol reduces blood pressure, at least in part, by mechanisms other than presynaptic beta-adrenoceptor blockade.

Adrenalectomy↗
PubMedDate not supplied

Blood pressure and heart rate response to central beta-blockade in conscious rats with glucocorticoid-induced hypertension.

The beta-adrenergic antagonist propranolol, administered subcutaneously to conscious adrenalectomized rats made hypertensive by exogenous glucocorticoids, has been shown to induce acutely a marked fall in blood pressure and heart rate. These animals almost completely lacked circulating epinephrine. Because both changes were closely related, it was suggested that in this model of hypertension propranolol acts via a central mechanism. To test this hypothesis, we now administered sotalol (300 micrograms) intracerebroventricularly to unanesthetized adrenalectomized rats with glucocorticoid-induced hypertension (this hydrophilic beta-blocking agent does not cross the blood-brain barrier). The same experiments were also performed in sham-operated glucocorticoid-hypertensive rats. On the day of the study, there was no significant difference between adrenalectomized and sham-operated groups of rats in intraarterial pressure and heart rate. Sotalol increased blood pressure and significantly slowed heart rate during the 60-min observation period, both in adrenalectomized and sham-operated rats. Sotalol's vehicle had no blood pressure effect and caused a transient heart rate acceleration in rats with, as well as without, circulating epinephrine. These results therefore suggest that the previously observed enhanced effect of peripherally administered propranolol in the absence of detectable circulating epinephrine, in this model, is not mediated centrally.

Adrenalectomy↗