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Biomedical subjects

J I Drayer

Publications and source records attributed to J I Drayer.

108 records · Page 6Linked to original sources
PubMed1976

Unexpected pressor responses to propranolol in essential hypertension. An interaction between renin, aldosterone and sympathetic activity.

The blood pressure response to propranolol treatment was analyzed retrospectively in 187 patients with benign essential hypertension. In most patients (102 patients, 54 per cent) systolic and/or diastolic blood pressure was decreased by more than 10 per cent (responders). No significant change in blood pressure occurred in 35 per cent (65 patients) of the patients (nonresponders). Surprisingly, in 20 patients (11 per cent) systolic (8 patients) and/or diastolic (14 patients) blood pressure was increased by more than 7 per cent (pressor-responders). All three subgroups received similar amounts of propranolol and irrespective of the effect on the blood pressure, propranolol produced a similar reduction in pulse rates, suggesting similar degree of beta blockade. The three subgroups did not differ in their clinical characteristics, except that the nonresponders were significantly older than the responders. Pretreatment renin values were highest in the responders, somewhat lower in the nonresponders and significantly lower in the pressor-responders. In a representative subset of 66 patients, control and treatment values for plasma renin activity and aldosterone excretion were compared. The responders had the most pronounced decreases in both renin and aldosterone. In striking contrast, no significant changes were observed in the two hormones in those patients whose blood pressure levels rose. Moreover, in the pressor-responders, the drug produced the greatest increases in body weight, reflecting sodium retention. The differences in blood pressure responses observed in different patients may be explained by various interplays between the drug-induced suppression of renin and aldosterone, and the operation of unapposed or reactive alpha sympathetic activity. The latter is presumably active in all patients tending to cause vasoconstriction and hence an increase in peripheral resistance. In the pressor-responders such unopposed alpha-tone combined with the demonstrated lack of renin and aldosterone suppression with attendant fluid retention could work to produce the paradoxical pressor responses. In contrast, in those whose blood pressure levels drop, the drug-induced suppression of renin leads to decreased peripheral resistance despite the unopposed alphatone. The accompanying decrease in aldosterone limits sodium retention and contributes to the fall in blood pressure levels.

Adult↗
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↗
PubMed1976

Triamterene-induced changes in aldosterone and renin values in essential hypertension. Evidence of a role for aldosterone in preventing blood pressure reduction.

The effect of triamterene, a potassium-retaining natriuretic and diuretic agent, on arterial blood pressure was studied in 31 patients with essential hypertension; there were seven patients with low plasma renin activity and 24 patients with normal plasma renin activity. Triamterene exhibited mild antihypertensive action, somewhat more pronounced in the low-renin group. The patients were also analyzed by considering them in terms of their blood pressure response. Of the 21 patients in the nonresponder group, no blood pressure decrease occurred, despite induced volume depletion accompanied by an increased plasma renin activity and a concomitant rise in the aldosterone excretion. In contrast, the ten patients in the responder group exhibited a fall in blood pressure, but the aldosterone excretion rate did not change significantly, even though plasma renin activity increased significantly. Moreover, only in the nonresponder group did the stimulated aldosterone excretion rate correlate significantly with the stimulated plasma renin activity. Thus, the failure of triamterene to lower blood pressure in the nonresponder group can be closely related to a significant increase in aldosterone excretion rate. The data suggest the operation of a reactive pressor action mediated by aldosterone, independent of its sodium-retaining effect.

Aldosterone↗
PubMed1975

Intrapatient comparison of treatment with chlorthalidone, spironolactone and propranolol in normoreninemic essential hypertension.

The effects of chlorthalidone, spironolactone and propranolol in reducing blood pressure were compared in the same 11 normoreninemic hypertensive patients. All three drugs decreased the blood pressure significantly and no agent had a superior blood pressure-lowering effect. The blood pressure did not normalize. The data suggest that no one variable--volume factors, relative hyperactivity of the renin-aldosterone system or beta-adrenergic hyperactivity--is the prime mover in normoreninemic hypertension. Long-term treatment with chlorthalidone resulted in slight hyperreninism (26.3 +/- 4.9 ng-ml-1-3 hours-1) (mean +/- standard error) with concomitant changes in plasma aldosterone (23.0 +/- 3.2 ng-100 ml-1). The body weight decreased significantly (--1.8 kg, P less than 0.005). Plasma potassium concentrations were low (3.2 +/- 0.1 mEq-liter -1). Creatinine clearance was unimpaired (117 +/- 6 ml-min-1). Treatment with spironolactone resulted in more marked hyperreninism (47.0 +/- 14.3 ng-ml-1-3 hours-1) and hyperaldosteronism (61.9 +/-11.8 ng-100 ml-1). The body weight decreased significantly (--1.9 kg, P less than 0.004). Significant hyperkalemia occurred (4.4 +/- 0.1 mEq-liter-1). The glomerular filtration rate decreased significantly to 93 +/- 3 ml-min-1 (P less than 0.004). Treatment with propranolol resulted in marked suppression of the plasma renin activity (1.8 +/- 0.2 ng-ml-1-3 hours-1) and plasma aldosterone levels (8.9 +/- 1.3 ng-100 ml-1). A significant increase in body weight occurred (+2.3 kg, P less than 0.013). The plasma potassium concentration increased to a level not significantly different from the value found after treatment with spironolactone (4.2 +/- 0.1 mEq-liter-1). The creatinine clearance decreased significantly to 99 +/- 5 ml-min-1 (P less than 0.008). Hyperreninemia (by spironolactone and chlorthalidone), effective hyperaldosteronism (by chlorthalidone) and volume retention (by propranolol) are considered to represent expressions of mechanisms counteracting the depressor effects of these different pharmacologic maneuvers, leading to the maintenance of supranormal blood pressure.

Adult↗
PubMed1975

The reliability of the measurement of plasma renin activity by radioimmunoassay.

A radioimmunoassay of angiotensin I has been applied to the measurement of plasma renin activity. Angiotensin I was generated in plasma samples by 3 h incubation at 37 degrees C and pH 5.6 after addition of EDTA and Dowex. The generated amount of angiotensin I was measured by radioimmunoassay in the eluate of the Dowex column. With this method a negligible amount of angiotensin I was measured after incubation at 4 degrees C (0.8 ng/ml per 3 h). Eluate of blank plasma had no measurable effect on the standard curve. The mean recovery of angiotensin I was 87%. The limit of detection of the assay was 0.5 ng/ml per 3 h. The results obtained using different antisera were equal. A marked variation was found in immunological properties of different standard preparations of angiotensin I tested. The mean value of angiotensin I generation per Goldblatt Unit (G.U.) renin was 3.9 with 10-4 ng/h. In normotensive control subjects, the plasma renin concentration, whileon unrestricted diet and after 3 h of ambulation, was on average 0.39 with 10-minus 4 G.U./ml, range 0.12 with 10-minus 4-0.91 with 10-minus 4. With the use of the same plasma extracts for radioimmunoassay and bioassay, a perfect correlation was found between the plasma renin activities measured with both assays. The differences found between the results of both assays could be fully explained by the different biological activities of the standards used (Angiotensin I, Schwarz Mann, and Angiotensin II, Ciba-Geigy). With a direct radioimmunoassay, angiotensin I was generated in plasma by 3 h incubation at 37 degrees C and pH 5.6 after addition of phenylmethanesulfonyl fluoride, 8-hydroxyquinoline and 2,3-dimercaptopropanol (dimercaprol). The generated amount of angiotensin I was measured by the above mentioned radioimmunoassay. A fairish correlation was found between the generated amounts of angiotensin I measured in the Dowex eluate and those found in the incubated plasma. Especially in the lowest range, lower values were obtained by the latter assay. However, the generated amounts of angiotensin I measured in non-incubated plasma samples (3 h at 4 degrees C) was on average 6.4 ng/ml per 3 h and accounted for 748% of the amounts found after incubation at 37 degrees C.

Angiotensin II↗
PubMed1975

Detection of low-renin hypertension; evaluation of out-patient renin-stimulating methods.

1. Three-renin-stimulating methods for detection of low-renin hypertension have been compared. First, renin activity was measured in hospital patients after 5 days of sodium restriction and 3 h ambulation. Secondly, renin activity was measured after frusemide stimualtion [0.42 mmol (140 mg) in 18 h] and 3 h ambulation. Thirdly, renin activity was measured after 5 days of chlorthalidone treatment [0.3 mmol (100 mg/day]ured after 5 days of chlorthalidone treatment [0.3 mmol (100 mg)/day] and 3 h ambulation. The last two tests were done with the subjects as out-patients without any dietary regimen. 2. In eleven normotensive control subjects and twenty hypertensive patients the results after frusemide were not comparable with those after sodium restriction since the frusemide test did not identify the same renin-suppressed hypertensive subjects as the sodium-restriction procedure. 3. After 5 days of chlorthalidone treatment in the renin values in eleven control subjects as well as in thirty-eight hypertensive patients were significantly higher than after sodium restriction. The values obtained after each procedure were closely correlated. 4. Thus the out-patinet chlorthalidone procedure identified similar sub-groups of patients as having low- or normal-renin hypertension as did the inpatient sodium-restriction test.

Blood Pressure↗
PubMedDate not supplied

The combined alpha- and beta-adrenergic blocker labetalol and propranolol in the treatment of high blood pressure: similarities and differences.

Labetalol, an agent with both alpha- and beta-adrenoreceptor blocking properties, and the beta blocker propranolol were each given for one month to groups of 15 patients with essential hypertension. With either treatment, 11 of the 15 patients experienced decreased supine diastolic blood pressure to less than 90 mm Hg without evidence of fluid retention. Propranolol significantly increased plasma concentrations of uric acid and potassium, whereas labetalol significantly increased plasma concentration of high-density lipoproteins (HDL) and decreased the total cholesterol:HDL ratio; neither drug significantly changed renal function. During three additional months of labetalol treatment, there was a slight tendency to orthostatic decreases in systolic blood pressure as compared with the values after the initial month. Labetalol had variable effects on plasma renin activity and aldosterone excretion, but within individual patients the values were constant; there were close correlations between changes measured after one month and after four months for both renin (r = 0.86) and aldosterone (r = 0.94). The manifestations of labetalol's alpha-blocking component appeared to be a small postural effect on systolic blood pressure and an increase in plasma HDL.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Low and high renin essential hypertension: a comparison of clinical and biochemical characteristics.

Based on a renin-sodium nomogram, patients with essential hypertension can be divided into low, normal and high renin subgroups. To define more clearly the clinical and biochemical characteristics of the two extreme groups, data of 83 patients with low renin essential hypertension were compared with those from 42 patients with high renin essential hypertension. In a further analysis, data or 27 age-and sex-matched patients from these two groups were compared with data from 27 matched subjects from a normotensive control group. Compared with high renin patients, low renin patients more frequently are female, older, and have higher systolic blood pressures and pulse pressures. The latter two characteristics are age-related. The similarity of duration of hypertension in both groups and the lack of correlation between age and plasma renin activity suggest that low renin hypertension is a separate entity rather than just a later phase of the same disease. Patients with low renin hypertension had better renal function than high renin patients or normotensive control subjects. High renin patients showed signs of hemoconcentration: hemoglobin, hematocrit, and total protein were higher than in low renin patients and normotensive controls. A significant difference between the slopes of the regression lines relating renin activity and sodium excretion for the two renin subgroups indicates that renin release in low renin patients is less sensitive to alterations in sodium balance. Both groups of patients had similarly elevated aldosterone levels, suggesting an increased sensitivity of aldosterone secretion to angiotensin II in low renin hypertensives. The relationship between aldosterone and potassium excretion was similar in both groups, indicating a comparable mineralocorticoid sensitivity.

Adult↗
PubMedDate not supplied

Combined central and peripheral sympathetic blockade: absence of additive antihypertensive effects.

Two antihypertensive agents that inhibits sympathetic activity by differing pharmacologic mechanisms, the centrally-acting alpha-adrenergic agonist, clonidine, and the peripheral alpha-adrenergic antagonist, prazosin, were compared and also given in combination in 24 patients with essential hypertension. The patients were randomized into two groups; 11 received chlorthalidone (50 mg) daily throughout the protocol, whereas 13 received no diuretic. In the 13 patients not receiving the diuretic, supine mean blood pressure fell by 11.0 +/- 3.5 mmHg (p less than 0.01) with clonidine (0.3 mg daily), 5.5 +/- 2.9 mm Hg (p less than 0.05) with prazosin (15 mg daily), and 12.7 +/- 5.2 mmHg (p less than 0.02) with the combination. In the 11 patients concurrently receiving chlorthalidone, supine mean blood pressure fell by 9.5 +/- 2.0 mmHg (p less than 0.01) when clonidine was added, 2.3 +/- 1.9 mmHg (ns) when prazosin was added, and 7.9 +/- 2.1 mmHg (p less than 0.01) with the combination. In both the presence and absence of concurrent diuretic treatment, the blood pressure-lowering effects of clonidine were greater than those of prazosin, but were not different from the antihypertensive effects of the combination of clonidine and prazosin. Therefore, the simultaneous administration of clonidine and prazosin in the doses used in this study does not appear to be more effective than clonidine alone in the treatment of patients with hypertension.

Adult↗
PubMedDate not supplied

Left ventricular hypertrophy and function in high, normal, and low-renin forms of essential hypertension.

To assess the relative importance of the level of blood pressure (BP) and renin profile status as determinants of hypertensive left ventricular hypertrophy (LVH) and dysfunction, we studied, by quantitative echocardiography, 118 hypertensive patients off medication. The 19 high-renin patients were younger (31 +/- 13 years; p less than 0.01) but had hypertension of severity (152 +/- 13/95 +/- 11 mg Hg) similar to the 79 normal-renin patients (42 +/- 14 years; 152 +/- 17/98 +/- 12 mg Hg) and 20 low-renin patients (49 +/- 13 yrs; 157 +/- 17/95 +/- 11 mm Hg). Left ventricular (LV) mass index (normal = 70 +/- 25 g/m2) was similar in the high- (113 +/- 21 g/m2, p less than 0.001), normal = (114 +/- 31 g/m2, p less than 0.001), and low-renin patients (115 +/- 18 g/m2, p less than 0.01). End-diastolic relative wall thickness (nl = 0.32 +/- 0.05) was equally elevated in high- (0.41 +/- 0.09), normal (0.42 +/- 0.08) and low-renin groups (0.41 +/- 0.08) (all p less than 0.001). In the entire population, there was a closer correlation of relative wall thickness with total peripheral resistance (r = 0.54, p less than 0.001) than with mean blood pressure (r = 0.31, p less than 0.05). LV dysfunction (LV fractional systolic shortening less than 26%) occurred only in two high-renin patients, whereas LV fractional shortening was significantly increased in the low-renin subgroup (p less than 0.01). We conclude that the degree of LVH is similar in low-, normal-, and high-renin hypertensives and is proportional to the degree of hypertension, even though the high-renin patients were significantly younger; but that the low-renin patients with similar level of blood pressure, even though significantly older and with a longer duration of hypertension than the other patient groups, manifest increased LV function compared to normals.

Adult↗
PubMedDate not supplied

Monotherapy of essential hypertension with a converting-enzyme inhibitor.

The antihypertensive effectiveness of twice-daily dosing with the converting enzyme inhibitor, captopril, was examined in a multicenter study of 294 patients (181 white, 111 black, two oriental) with essential hypertension whose supine diastolic blood pressure (SDBP) was 95 mm Hg or higher after 4 to 6 weeks of preliminary placebo administration. In this double-blind study, the patients were randomized into one placebo and three captopril-treated groups: twice-daily placebo (n = 77) or twice-daily captopril 25 mg (n = 77), 50 mg (n = 71), or 100 mg (n = 69). The average decreases in SDBP after 8 weeks of treatment were 5.2%, 7.7%, 11.7%, and 10.5%, respectively. Only the two higher dose groups differed significantly from the placebo group; they also differed from the lowest dose group. The proportions of patients classified as having normalized pressures (SDBP less than 90 mm Hg) in the four groups were 39%, 47%, 70%, and 50%. If the results were analyzed by race, all three captopril-treated groups differed significantly from the placebo-treated group in the white patients but not in the black patients. However, direct comparisons between the white and black groups showed a difference only at the low, 25 mg twice daily (b.i.d.), captopril dose. Thus, although conventionally given on a three-times daily basis, the twice-daily (12-hourly) administration of captopril provides effective antihypertensive treatment in doses of 50 or 100 mg b.i.d. Moreover, white patients also exhibit a significant response to captopril at doses as low as 25 mg b.i.d.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗