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Biomedical subjects

H Herlitz

Publications and source records attributed to H Herlitz.

At least 55 records · Page 3Linked to original sources

Renal and systemic sympathetic counterregulation in response to vasodilators in renovascular hypertension.

1. Twenty-two patients with renovascular hypertension and significant lateralization of renin secretion were investigated with respect to arterial and renal venous plasma noradrenaline and dopamine concentrations before and 30 min after two different blood pressure-lowering procedures (enalaprilat or dihydralazine intravenously). 2. In one group of patients (n = 10) blood pressure reduction by 7.5 mg of dihydralazine caused stimulation of the renin-angiotensin system and increased heart rate (P < 0.01) as well as arterial and renal venous plasma noradrenaline and dopamine concentrations (P < 0.01 for both). The elevation of the plasma dopamine concentration was more pronounced than that of noradrenaline, yielding increased dopamine/noradrenaline ratios both peripherally (P < 0.05) and in the renal veins (P < 0.05). 3. In the second group of patients (n = 12) a comparable reduction in blood pressure elicited by 1.25 mg of enalaprilat was not accompanied by alterations in heart rate or in noradrenaline or dopamine levels in arterial plasma or renal venous plasma from either kidney. 4. Thus, inhibition of angiotensin-converting enzyme does not elicit the expected sympathetic counter-regulatory response to blood pressure reduction; the mechanism(s) involved remains to be clarified.

Adolescent↗

Microalbuminuria in treated hypertensive men at high risk of coronary disease. The Risk Factor Intervention Study Group.

OBJECTIVE: To examine whether microalbuminuria is a marker of cardiovascular disease in treated hypertensive men without diabetes mellitus at high coronary risk and to examine the associations between microalbuminuria and recognized cardiovascular risk factors. DESIGN: Cross-sectional study. SETTING: Outpatient clinic in city hospital. PATIENTS: Three hundred and thirty-three treated hypertensive men, aged 50-72 years, either with a serum cholesterol of > or = 6.5 mmol/l or smokers, or both. The patients were recruited mainly from a population-based sample of hypertensive men. Patients with diabetes mellitus or overnight urinary albumin excretion of > 100 mg/12 h were excluded from the analyses. MAIN OUTCOME MEASURES: Overnight urinary albumin excretion, prevalence of microalbuminuria (defined as 17-100 mg/12 h) and organ damage (cardiovascular events or major electrocardiogram changes, or both), various well-established risk factor levels, blood glucose and plasma insulin responses to an oral glucose tolerance test. RESULTS: Microalbuminuria was found in 25% of the cohort. Among microalbuminuric patients, organ damage was significantly more common (47.6%) than in the normoalbuminuric group (30.9%). However, the sensitivity and specificity of microalbuminuria as a marker of organ damage were only 34 and 80%, respectively. Microalbuminuria was significantly related to body mass index and waist:hip ratio, age and plasma insulin during oral glucose tolerance testing. These relationships also persisted after adjustment for treatment with thiazides or beta-blockers. CONCLUSIONS: In treated hypertensive men without diabetes mellitus, microalbuminuria was associated with factors known to be related to insulin resistance. It had a low sensitivity as a marker of concomitant cardiovascular disease.

Aged↗

Abnormal immune function in malignant hypertension.

OBJECTIVE: To investigate the extent to which the immune system is influenced in patients with previous malignant hypertension. DESIGN: Twenty-three patients with malignant hypertension (fundus hypertonicus grades III or IV) in the Gothenburg area were studied over a 3-year period. After treatment had been instituted they were investigated to establish the function of the cellular immune system (number of T lymphocytes and the proliferative response to T-cell mitogens), human leucocyte antigens A, B and C and frequency of autoantibodies. METHODS: The numbers of T lymphocytes were quantified as erythrocyte rosettes. Lymphocyte-stimulation tests were carried out using the T-cell mitogens phytohaemagglutinin and concanavalin-A. Autoantibodies were determined with immunoassay techniques and leucocyte A, B and C antigens with a lymphocytotoxicity test. RESULTS: The frequency of T lymphocytes and their baseline thymidine incorporation were significantly depressed in patients with previously malignant hypertension compared with control subjects. The group with malignant hypertension also had a decreased proliferative response to concanavalin-A but not to phytohaemagglutinin, and they had an increased frequency of antinuclear antibodies. Human leucocyte antigen B15 tended to occur more frequently in patients with malignant and non-malignant hypertension than in control subjects, especially if a family history of hypertension was taken into consideration. CONCLUSION: The results from the present study indicate that immune mechanisms are involved in malignant hypertension, either secondary to the vascular damage or as a primary abnormality.

Antibody Formation↗

Altered erythrocyte transmembrane transport of sodium and potassium in patients with conventional or reservoir ileostomy.

After proctocolectomy, the loss of the colonic absorptive capacity of sodium is compensated for by increased small intestine sodium absorption and renal conservation of Na by enhanced tubular reabsorption. These processes entail increased cellular sodium transport in the enterocytes and in the renal tubular cells. In order to evaluate if there is a general increase in cellular transport of Na after proctocolectomy for inflammatory bowel diseases erythrocyte Na and K contents and the transmembrane Na fluxes were determined in 35 patients with conventional ileostomy, 23 of which were reinvestigated after conversion to continent reservoir ileostomy. A selected group of another 12 patients having high output from their reservoir ileostomy and low urinary Na were studied concomitantly and 33 healthy subjects served as controls. The intracellular Na content did not differ between the groups while the intracellular K levels were higher in patients with conventional or continent ileostomy compared to controls. In addition, the Na influx and the efflux rate constant of Na were both increased after conversion to reservoir ileostomy. Na influx correlated positively with intake and urinary excretion of Na in conventional ileostomy patients. The results suggest that patients with ileostomy have an increased cellular K uptake and that construction of a reservoir ileostomy further alters cell cation transport by increasing the transmembrane Na turnover.

Adult↗

A comparative study of lisinopril and atenolol on low degree urinary albumin excretion, renal function and haemodynamics in uncomplicated, primary hypertension.

The presence of slightly increased urinary albumin excretion (UAE), even at levels well below levels detectable by an ordinary dipstick, has been suggested as a predictor of cardiovascular morbidity and as a reflection of the degree of overall vascular permeability. The aim of the present investigation was to study the effects of two different antihypertensive drug regimens, an ACE inhibitor and a beta-adrenoceptor antagonist, on the low UAE rate observed in subjects with uncomplicated, mild to moderate primary hypertension. After a 4-week placebo run-in period, 49 patients (mean age 54 y) were randomly assigned in a double blind manner either to further 4 weeks on placebo (P, n = 15), 8 weeks on lisinopril (L, n = 17; 20 mg/40 mg o.d.) or 8 weeks on atenolol (A, n = 17; 50 mg/100 mg o.d.). The 24-h UAE was measured every second week. At entry and after 4 weeks the glomerular filtration rate and the renal plasma flow were measured. Both drugs lowered blood pressure (BP) to a similar extent after 4 and 8 weeks of treatment; the blood pressures were 160/106 (P), 159/104 (L) and 154/103 (A) at entry, and 133/83 (L) and 134/87 (A) at the end of the study after 8 weeks. On entry the 24-h UAE in all patients ranged from 4 to 49 mg (mean 14.1 mg), and it did not differ significantly between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Reversal of cardiovascular structural changes when treating essential hypertension. The importance of the renin-angiotensin-aldosterone system.

Our study attempted to evaluate the importance of changes in the circulating renin-angiotensin-aldosterone system (RAAS) and in hemodynamics in relation to observed changes in cardiovascular structure. We studied previously untreated men (n = 28) with essential nonmalignant hypertension and a supine casual diastolic blood pressure > 95 mm Hg on three to four separate (> 1-week interval) occasions measured in triplicate. We used intraarterial blood pressure, dye-dilution technique, plethysmography (hands), eye-ground photos, M-mode echocardiography, radio immunoassays, and multiple regression analysis. Patients were randomized to 6 months of double-blind treatment with either enalapril or hydrochlorothiazide, following 4 to 6 weeks on placebo. We found that enalapril blocked the plasma angiotensin converting enzyme (ACE) with a secondary increment in plasma renin activity (PRA) and reductions in angiotensin II (AII) and aldosterone. Blood pressure was lowered through a reduction in total peripheral resistance (TPR). Hydrochlorothiazide increased PRA, AII, and aldosterone, and lowered blood pressure mainly through a reduction in cardiac output. Enalapril was significantly more effective than hydrochlorothiazide in reversing structural changes in the retinal and hand vasculature as well as in the heart. A reduction in cardiac hypertrophy was seen even in the occasional enalapril-treated patient, in whom little or no reduction in blood pressure occurred. In the stepwise regression analyses, the changes in retinal and hand vascular structure were most strongly related to various changes in the RAAS, explaining 15 to 34% of the variance. For the changes in cardiac structure, the type of therapy (enalapril or hydrochlorothiazide) appeared to be the most important factor, explaining between 29 and 50% of the variance. The changes in cardiac structure were even more strongly related to changes in the RAAS for the enalapril treated patients and explained up to 55% of the variance in cardiac structure. It can be concluded that the reversal of structural vascular changes during antihypertensive therapy was more dependent on the blockade of the RAAS than on lowering of the blood pressure.

Blood Pressure↗

Increased systemic and renal vascular sensitivity to angiotensin II in normotensive men with positive family histories of hypertension.

Normotensive young men (mean age 36 years) with positive (PFH) (n = 13) and negative (n = 29) family histories of hypertension were investigated in order to study systemic and renal hemodynamics at baseline conditions and during infusion of low doses (0.1 and 0.5 ng/min/kg) of angiotensin II (AII). The control group with negative family histories of hypertension was subdivided into one group matched for body mass index (n = 15) to subjects with PFH, and one lean control group (n = 14). Baseline blood pressure and sodium intake, measured as urinary excretion, were higher in PFH and in matched controls than in the lean control group. At baseline, renal blood flow (para-aminohippurate clearance) did not differ significantly among the three groups, while glomerular filtration rate (inulin clearance) was higher in PFH than in matched controls. Both doses of angiotensin II infusion increased the blood pressure significantly in PFH. In matched controls a small increase in blood pressure was seen with the highest dose only, while no change in blood pressure was observed in the lean control group. In PFH both doses of AII infusion caused diminished renal blood flow (P less than .01) and increased renal vascular resistance (P less than .001). The two control groups remained unchanged with both AII doses. These results could indicate that normotensive subjects with positive family histories of hypertension are characterized by an increased sensitivity to AII in the systemic and renal circulation as compared with subjects with negative family histories of hypertension.

Adult↗

Increased waist/hip ratio, metabolic disturbances, and family history of hypertension.

To test whether nonhypertensive subjects with a two-generation positive family history of hypertension (PFH) are characterized by disturbed glucose metabolism, 16 men (38 +/- 6 years old) with PFH and 25 subjects matched for age and with negative family histories of hypertension (NFH) were recruited. Blood pressure; serum lipids; erythrocyte transmembrane sodium transport; and the glucose, plasma insulin, and C-peptide responses to an oral glucose tolerance test were investigated. Subjects with PFH had higher blood pressure, body weight, body mass index (BMI), waist/hip ratio (WHR), and abdominal sagittal diameter than subjects with NFH. Baseline blood glucose, plasma insulin, serum lipids, and transmembrane sodium transport did not differ between the two groups. Blood glucose levels at 90 and 120 minutes after oral glucose were significantly higher in subjects with PFH than in controls. Blood glucose adjusted for BMI and WHR at 90 minutes was significantly related to a PFH. Plasma insulin level at 90 minutes during the glucose load was significantly higher in subjects with PFH. In multivariate analysis, WHR was significantly related to baseline blood pressure, insulin, and cholesterol, whereas BMI was significantly associated with the insulin response to the oral glucose tolerance test. Transmembrane sodium transport was significantly related to blood pressure only. In conclusion, subjects with PFH are characterized by increased body weight and BMI, increased visceral fat accumulation, and an altered blood glucose response to an oral glucose load. It was also shown that WHR was related to blood pressure and that BMI was more related to cholesterol and response to glucose loading than a PFH was.

Adult↗

Relationship between plasma growth hormone concentration and cellular sodium transport in acromegaly.

We investigated the relationship between mean plasma growth hormone (GH) concentration and cellular sodium transport in untreated and treated acromegaly. Seventeen patients (age 55 +/- 3 years) with active acromegaly were studied with respect to plasma GH (mean of 24 h GH profile) and erythrocyte electrolyte content as well as transmembrane sodium transport. The patients were reinvestigated two weeks after successful surgery (N = 14) and again after one year (N = 13). Erythrocyte electrolytes were analyzed by flame photometry and sodium influx and efflux rate constant determined by in vitro incubation using a modified Keyne's formula. In patients with active acromegaly there was a significant positive correlation between IGF-1 and cellular sodium transport, while GH tended to show a negative relationship to the same parameter. After successful treatment, both IGF-1 and GH disclosed a positive relationship to cellular sodium transport. After one year, a significant increase in erythrocyte sodium content was seen in the patients compared to the preoperative situation. In conclusion, if this is a generalized phenomenon the results are compatible with a sodium-retaining effect of GH via stimulation of transmembrane sodium transport. In active acromegaly this may be counteracted by a sodium transport inhibitor giving the reverse relationship between GH and cellular sodium transport.

Acromegaly↗

Urinary kallikrein excretion is low in malignant essential hypertension.

OBJECTIVE: To determine whether the urinary excretion of kallikrein is altered in patients with previously malignant hypertension. DESIGN: Twenty-two patients with malignant hypertension (fundus hypertonicus III or IV) in the Gothenburg area were studied over a 3-year period. After treatment had begun they were investigated for blood pressure control, family history of hypertension, renal function and urinary kallikrein and plasma prekallikrein concentrations. Twenty-two patients with treated non-malignant hypertension and 36 control subjects were investigated concomitantly. The two hypertensive groups were also separated into subgroups of essential and secondary hypertension. METHODS: Prekallikrein was activated and kallikrein determined by a spectrophotometric assay using a synthetic chromogenic substrate. Renal function was estimated by serum creatinine and 51Cr-ethylenediaminetetraacetic acid clearance. RESULTS: Prekallikrein levels tended to be elevated in all groups of hypertensive patients compared with controls whilst urinary kallikrein was significantly decreased in malignant hypertensives. The most pronounced suppression of urinary kallikrein was seen in the group of patients with essential malignant hypertension. The differences persisted when urinary kallikrein was related to the degree of renal impairment or when urinary volume was taken into account. There was no relation between family history of hypertension and low levels of urinary kallikrein. CONCLUSION: Decreased urinary kallikrein could indicate depressed activity in the renal kallikrein-kinin system, which may be associated with the initiation of essential malignant hypertension.

Antihypertensive Agents↗

Effect of captopril treatment on allograft survival and induction of unresponsiveness in heart-transplanted, ATG-treated rats.

The angiotensin-converting enzyme inhibitor captopril has been suggested to have an immunomodulatory effect both in clinical and experimental studies. To further investigate this possible effect in organ transplantation, captopril was given to inbred rats before transplantation of an allogeneic heart. Captopril was found to prolong graft survival significantly compared to untreated controls. In rats treated with a tolerogenic dose of ATG, additional captopril administration tended to increase the proportion of rats with long-term functioning grafts, but this did not reach statistical significance. It is concluded that captopril displays an immunosuppressive effect that seems to be weak, since no augmentation of ATG-induced transplantation unresponsiveness was seen.

Animals↗

Long-term effects of felodipine in patients with reduced renal function.

To characterize the long-term effects of calcium antagonists on renal function in hypertension felodipine was used to treat 14 patients with severe uncontrolled hypertension associated with renal functional impairment: six patients had renal parenchymal hypertension, six had essential hypertension and two had renovascular hypertension. Mean blood pressure was 197 +/- 2/115 +/- 3 mm Hg despite treatment with three or more antihypertensive drugs. Mean glomerular filtration rate (GFR) was 39 +/- 6 ml/min (Cr-EDTA clearance) before initiation of felodipine treatment. All patients experienced a blood pressure reduction after starting felodipine treatment, which persisted during long-term therapy in combination with previous medication except former vasodilating drugs. Blood pressure after 12 and 24 months was 152 +/- 7/89 +/- 2 and 157 +/- 5/90 +/- 2 mm Hg, respectively. Patients with moderately impaired GFR and absence of progressive renal disease (N = 8) manifested an increase in GFR after 6 and 12 months on felodipine (59 +/- 10 to 63 +/- 7 and 70 +/- 6 ml/min, respectively, P less than 0.05). Renal plasma flow (PAH clearance) exhibited only a slight increase (315 +/- 68 to 340 +/- 63 and 314 +/- 69 ml/min) with a consequent increase in filtration fraction (18 +/- 1 to 21 +/- 1 and 20 +/- 1%, NS). At follow-up after six to eight years patients with initial GFR greater than or equal to 50 ml/min had a maintained renal function. In five patients a progressive deterioration of renal function had been documented.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Blunted renal sodium excretion during acute saline loading in normotensive men with positive family histories of hypertension.

The natriuretic and intra-arterial blood pressure response to an acute saline load (1000 mL 0.9% NaCl), was studied in normotensive young men with positive (n = 11) and negative (n = 21) family histories of hypertension. The age-matched (36 +/- 5 years) control group with negative family histories of hypertension was subdivided into two groups, one matched for body mass index (BMI) to the subjects with positive family histories of hypertension (n = 10), and another lean control group (n = 11). Baseline blood pressure was significantly higher in subjects with positive family histories of hypertension and in controls matched for BMI as compared with lean controls. Sodium excretion increased in all three groups during the saline infusion, while subjects with positive family histories of hypertension disclosed a diminished natriuretic response as compared with the two control groups. Systolic blood pressure increased significantly during the saline load in subjects with positive family histories of hypertension, while in subjects with negative family histories of hypertension, no significant change in blood pressure was observed. Plasma renin activity, angiotensin II, serum aldosterone, plasma noradrenaline, blood volume, and ouabain-sensitive erythrocyte sodium efflux rate constant did not differ between the three groups at baseline. A significant negative correlation was found between baseline sodium excretion and sodium efflux rate constant in subjects with positive family histories of hypertension. We conclude that the subjects with positive family histories of hypertension exhibit a blunted natriuretic and an exaggerated blood pressure response to an acute saline load as compared with the two control groups with negative family histories of hypertension. This could be of neuronal and/or hormonal origin.

Adult↗

Normotensive young men with family histories of hypertension gain weight and decrease their intraerythrocyte sodium content during a 5-year follow-up.

Young normotensive men matched for age and body mass index with (n = 16) and without (n = 13) family histories of hypertension were investigated at baseline and after 5 years of follow-up with respect to blood pressure, body weight and intracellular sodium content. Subjects with positive family histories of hypertension increased significantly in body weight (from 81.9 +/- 11.5 kg to 89.5 +/- 11.4 kg, P less than 0.001) compared to subjects with negative family histories of hypertension (from 79.9 +/- 10.8 kg to 80.7 +/- 12.2 kg, NS). Their blood pressure did not differ initially (137 +/- 12/75 +/- 11 mmHg vs. 135 +/- 8/72 +/- 9 mmHg), but was reduced in subjects without family histories of hypertension (to 125 +/- 3/68 +/- 13 mmHg) in the follow-up examination. At follow-up, body mass index showed a positive correlation with blood pressure among subjects with positive family histories of hypertension (r = 0.77, P less than 0.001). At baseline, subjects with hypertensive fathers had significantly higher intraerythrocyte sodium levels than subjects with normotensive parents. At re-examination 5 years later, this difference was no longer present. We conclude that normotensive subjects with positive family histories of hypertension are predisposed to gain weight rather than to show an increase in blood pressure at this age. Normalization of intracellular sodium content, as found in the present study, could be a consequence of this weight gain and the ensuing metabolic adaption.

Adult↗

Acute and long-term changes in plasma levels of atrial natriuretic factor in patients with renal replacement therapy.

In 14 patients on hemodialysis who received kidney grafts from living related donors, plasma levels of immunoreactive atrial natriuretic factor (Ir-ANF) were determined in a sequence covering the last hemodialysis treatment, the day of transplantation, and a follow-up period of 6-12 months. The geometric mean value before dialysis was 196 pg/ml, the range 32-634. Weight loss during dialysis was 1.5 +/- 1.1 kg (mean +/- SD), but only a nonsignificant reduction in Ir-ANF levels occurred. On the day of transplantation, plasma Ir-ANF levels increased from 143 pg/ml before to 391 post-transplantation (P = 0.02, n = 12), probably in response to deliberate volume expansion. Post-transplant Ir-ANF levels correlated significantly to diuresis during the first 24 h, which ranged from 3.7 to 17.81 (mean 6.6; r = 0.65, P = 0.02). On day 2, mean 24 h diuresis decreased to 3.3 +/- 1.41. Most patients had reached their true dry weight by day 5, but Ir-ANF levels remained high, the geometric mean being 180 pg/ml. During further follow-up and preserved graft function (GFR range 34-88 ml/min per 1.73 m2 body surface area), Ir-ANF levels declined to a geometric mean of 63 pg/ml by 2-6 months and to 36 at 12 months post-transplant. We conclude that plasma Ir-ANF levels are chronically elevated in patients with chronic renal failure but may be further stimulated by acute overhydration. Transplanted kidneys initially respond to the increased levels but adapt within a day. Even with good graft function, normalization of plasma Ir-ANF requires several weeks or months.

Adolescent↗