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Biomedical subjects

J M Wallace

Publications and source records attributed to J M Wallace.

At least 145 records · Page 8Linked to original sources
PubMed1978

Prazosin in the diagnosis and treatment of pheochromocytoma.

In a patient with paraganglioma, severe hypertension due to high levels of plasma norepinephrine was easily controlled with prazosin hydrochloride, 6 to 8 mg/day for 19 days before surgery. A prolonged antihypertensive response to the first two 1-mg doses suggested the presence of pheochromocytoma. This experience dramatizes the remarkable effectiveness of prazosin as a postsynaptic alpha-adrenergic receptor blocker and invites further trials of the drug for both the diagnosis and treatment of pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1978

Living with stress.

Explore the source record for details and available documents.

Adaptation, Physiological↗
PubMed1977

Possible role of renin in hypertension as suggested by renin-sodium profiling and inhibition of converting enzyme.

To block renin activity, a nonapeptide converting-enzyme inhibitor was given to 65 seated hypertensive patients. Depressor responses occurred only when control plasma renin activity exceeded 2 ng of angiotensin I per milliliter per hour and correlated directly in amplitude with control plasma renin activity and with induced increments in activity (P less than 0.001 for both). Depressor responses, like renin activity, were characteristic for renin subgroups as defined by renin-sodium profiling. Before and after sodium deprivation, the nonapeptide reduced diastolic pressure in all patients with high renin (by 17.3 and 19.8 per cent) and most patients with normal renin (by 9.1 and 17.7 per cent). Low-renin patients remained unresponsive. This enzyme blockade may cause bradykinin accumulation. But if, as seems likely, depressor responses are due to blockade of angiotensin II formation, the results indicate that, irrespective of sodium balance, measurements of plasma renin activity reflect its contribution to blood-pressure maintenance. The results suggest broad participation of the renin system in common forms of hypertension.

Angiotensin II↗
PubMed1977

Blockade of renin or angiotensin for understanding human hypertension: a comparison of propranolol, saralasin and converting enzyme blockade.

To understand the role of the renin-angiotensin-aldosterone system in the pathogenesis of human hypertension, in serial studies we have blocked the system using three different pharmacologic probes: 1) reduction of renin secretion by administration of the beta receptor blocker, propranolol; 2) blockade of the action of angiotensin II by infusion of saralasin, a competitive antagonist of angiotensin II; and 3) blockade of the enzymatic conversion of angiotensin I to angiotensin II by infusing a nonapeptide competitive inhibitor. The depressor responses induced by either propranolol or the nonapeptide expose a significant to major involvement of excess renin--angiotensin in maintaining the hypertension of some 50 to 70% of common forms of hypertension including "essential" hypertension. This subgroup includes nearly all patients with high or "normal" renin--sodium profiles. The considerably lower estimates for a renin factor in essential hypertension suggested by saralasin testing now appear due to the partial agonism of this drug. Further studies are required to determine whether this relative or absolute excess of renin secretion is primarily involved in the hypertension and if not why it fails to shut itself off. Similar studies of normal subjects are also needed to determine whether renin support of blood pressure is proportionately greater or less than in hypertensive subjects. Meanwhile the validation provided by these three different pharmacologic probes portends a burgeoning clinical role for renin--sodium profiling not only in screening for renal and adrenal cortical hypertensions but also for characterizing the vasoconstrictor and volume elements involved in various individual patients and thus enabling more specific treatments of the various subtypes of essential hypertension.

Aldosterone↗
PubMed1977

The immediate pressor response to saralasin: a measure of the degree of angiotensin II vascular receptor vacancy.

(1) An immediate pressor response so saralasin, 10 microgram/kg/min, occurred in 52 of 57 (91%) hypertensive patients. (2) We propose that the amplitude of the immediate pressor response functions as an in vivo measure of the number of initially vacan angiotensin II vascular receptors. (3) The immediate pressor response to saralasin forecasts the subsequent sustained response, both of which are related to the renin-sodium profile. (4) The dual blood pressure responses to saralasin, immediate and sustained, make this drug useful for the pharmacological identification of high, normal, and low renin hypertensive patients as they are presently classified. (5) The ability of saralasin to elevate the BP immediately in most hypertensive patients shows the need for caution in its use. It is a safe drug from this standpoint if very small infusions (0.01-0.10 microgram/kg/min) are first tried in hypertensive patients whose PRA is unknown.

Angiotensin II↗
PubMed1976

Usefulness and limitations of saralasin, a partial competitive agonist of angioten II, for evaluating the renin and sodium factors in hypertensive patients.

Saralasin was infused into 52 untreated hypertensive patients. Immediate, transient pressor responses occurred in 94 per cent followed by a more gradual sustained change in blood pressure reaching an apogee in about 20 minutes. Most (86 per cent) patients with high renin values had sustained depressor responses irrespective of sodium balance. In contrast, during a normal sodium intake, the drug produced a neutral (45 per cent) or mildly pressor (50 per cent) response in patients with normal renin and pressor responses in patients with low renin values. Sodium depletion abolished pressor responses and resulted in depressor responses in 64 per cent of the patients with normal renin values. The pretreatment angiotensin level appeared to determine direction and amplitude of the response to saralasin, since increases and decreases in diastolic pressure exhibited a highly significant relationship to the control renin lever (r = 0.80, p less than 0.001). Above a neutral range of control renin values, from 2 to 7 ng Al/ml/hour, depressor responses were the rule, and below it pressor responses were consistent. Sodium balance also appeared to determine the amplitude of the response. In a subset of patients with similar renin values (range 1.4 to 2.2 ngAl/ml/hour), the induced pressor responses correlated directly with the 24-hour sodium excretion (p less than 0.05). For all patients, the induced pressure change also was related to the rate of sodium excretion (r = 0.53, p less than 0.001). The data suggest that saralasin behaves as a partial competitive agonist of angiotensin II. For this reason, saralasin testing provided only a rough physiologic validation for renin profiling. Thus, depressor responses expose most patients with high renin values. Neutral responses occur in many patients with normal renin and intermediate renin values. But pressor responses occur in subjects with either low or normal renin levels and they may reflect sodium and volume excess associated with a partial or relative absence of renin. Accordingly, due to its partial agonism, saralasin testing under-estimates the renin factor. Hence, the drug cannot be used to identify or exclude renin involvement in the blood pressure in the large majority of hypertensive patients who do not exhibit depressor responses. For them an agent devoid of agonism is required. Moreover, prior sodium depletion as a device to increase the frequency of depressor responses to saralasin does not measure intrinsic renin dependency of the blood pressure but rather the reactivity of the system to sodium depletion.

Angiotensin II↗
PubMed1976

Estimating renin participation in hypertension: superiority of converting enzyme inhibitor over saralasin.

This study was designed to examine more closely the differences in blood pressure responses in hypertensive patients to two agents which block the renin-angiotensin system. Accordingly, 39 seated patients received under the same conditions both saralasin, an octapeptide competitive antagonist of angiotensin II, and the nonapeptide converting enzyme inhibitor, SQ20881, which blocks the generation of angiotensin II from angiotensin I. A second component of the study involved administration of these agents in 10 addtional studies in anephric subjects. Although both agents produced maximal responses in blood pressure that correlated well with each other (p less than 0.001) and with the pretreatment plasma renin levels (p less than 0.001), analysis of the results by renin subgroups revealed significant differences. Thus, both drugs lowered the diastolic pressures of patients with high renin levels, but but converting enzyme inhibitor produced changes of greater amplitude (p less than 0.05). In contrast, saralasin was consistently pressor in both patients with low renin levels and anephric patients in whom converting enzyme blockade preduced no significant changes in blood pressure. Another impressive disparity in the responses to the two agents occurred in the group with normal renin levels in whom saralasin produced either neutral or pressor responses (mean change was +2.0 +/- 1.5 standard error of the mean (SEM) per cent control diastolic pressure) whereas the converting enzyme inhibitor consistently induced depressor responses (mean change was -10.2 +/- 1.2 per cent, p less than 0.001). Altogether, the results suggest that converting enzyme inhibitor tests for angiotensin II-dependent blood pressure with more sensitivity than the partial agonist saralasin. Moreover, it is unlikely that the differences between the responses to the two agents were due to bradykinin accumulation, since depressor responses to converting enzyme inhibitor were not observed in the patients with low renin levels and the anephric patients.

Adolescent↗
PubMed1976

Impedance cardiography for determination of stroke index.

Stroke index obtained by impedance cardiography was compared with values obtained by dye-dilution technique in 17 subjects in 122 determinations made within 2 min of each other. Fifty of these determinations were done after drug administration, postural change, or saline infusion. All values obtained by both methods correlated significantly, but with wide scatter (r=0.49, n = 122, P less than 0.001). The series of determinations within each subject, however, correlated only in one subject significantly; thus any changes of stroke index measured by both techniques were not commensurate. In addition, the impedance stroke index values were significantly lower than the dye-dilution technique, impedance cardiography presently does not determine reliably absolute values of stroke index and is not suitable to evaluate changes of stroke index.

Adult↗
PubMed1975

Hemodynamic lesions in hypertension.

Essential hypertension is increasingly recognized as a nonhomogenous disorder by various methods of study. The hemodynamic approach, coupled with clinical determination of the range and lability of blood pressure, has resulted in the description of several subgroups: labile hypertension with normal or elevated cardiac output, fixed or established hypertension with varying cardiac output and advanced hypertension with normal or low cardiac output. There is a tendency to postulate that these categories are stages of one disorder, but this remains to be proved. Still other patients have been described who may be further set off by exceptionally labile or hyperkinetic features. In some hypertensive patients, the peripheral resistance is normal; however, regardless of its numerical value, it is now considered to be increased if it fails to decrease normally in the presence of elevated cardiac output. Because an elevated cardiac output is the hemodynamic function that differentiates these groups, and renovascular hypertension as well, it is the focus of much current work. New interest in the central blood volume, the peripheral veins, and the portal veins and splanchnic circulation is focused on their connection with cardiac out-put. Newly appreciated, too, is the existence of parasympathetic inhibition in hypertension, which not only contributes to elevations of heart rate, cardiac output and possibly renin secretion, but also depresses baroreflex responses. Thus far, hemodynamic and endocrine mechanisms of hypertension have not been studied together, except possibly through the blood volume, which remains a highly controversial topic. In this paper, some recent work in the above areas is reviewed and emphasis is given to studies in man.

Adrenergic beta-Agonists↗
PubMed1972

Spot test for lipoxygenase activity.

A qualitative iodometric test for lipoxygenase activity is described. The sensitive method is useful for rapidly screening large numbers of samples, as from a chromatography column or after enzyme inactivation treatment in food processing.

Catalase↗