Genetic influence on blood pressure and lipid parameters in a sample of Polish twins.

We studied 76 healthy monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs (mean age 35 +/- 8 years, body mass index, BMI, 23.6 +/- 3.9 kg/m2) to determine genetic and environmental contributions to systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR) and serum lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-chol), high-density lipoprotein cholesterol (HDL-chol) and triglycerides (TG)I. SBP, DBP and HR were measured clinically and by ambulatory blood pressure monitoring (ABPM). Parameters of the genetic models for age-, sex- and BMI-adjusted data were estimated by model fitting and path analysis technique using LISREL 8. We found significant genetic effect on SBP and DBP for both clinical and ABP measurements, ranging from 37% for night-time ambulatory DBP to 79% for daytime ambulatory SBP. Estimates of genetic effects were higher for daytime than night-time ABP values, and higher for ambulatory 24-h SBP than office SBP measurements, with the reverse true for DBP. Significant genetic effect on HR ranged from 59% for office measurements to 69% for 24-h mean values. In summary, we also found genetic effect on TC, LDL-chol and HDL-chol with estimates ranging from 36% to 64%, but not on TG. Furthermore, a shared environmental component for TG was found, estimated at 36%. We showed significant genetic effect on both office and ambulatory BP and HR, with stronger genetic effect on daytime than night-time BP. We also found genetic effect on TC and lipoprotein fractions, but no significant genetic effect on TG. Environmental factors influencing serum TG, such as alcohol consumption, may explain the apparent lack of genetic effect in this healthy, non-obese population.

Alterations in plasma neuropeptide Y immunoreactivity and catecholamine levels during surgical removal of pheochromocytoma.

BACKGROUND: Neuropeptide Y, an abundant neurohormone present with catecholamines in the adrenal medulla, is a potent non-adrenergic vasoconstrictor and a vascular growth factor. OBJECTIVE: To determine the mechanism of the release from, and possible role of neuropeptide Y in, pheochromocytomas, compared with those of catecholamines. METHODS: Plasma and tumour levels of neuropeptide Y-immunoreactivity (by, radioimmunoassay) and of noradrenaline and adrenaline (by a radioenzymatic method) in 29 patients (19 women and 10 men, aged 22-68 years) were measured during surgical removal of the tumour, during alpha-adrenergic and beta-adrenergic blockade. Arterial systemic blood samples were withdrawn before the ligation of the vessels supplying the tumour, during its surgical manipulations and after its removal, while haemodynamics was monitored. RESULTS: Plasma neuropeptide Y levels in 17 patients (58.6%, group I) significantly increased during manipulations of the pheochromocytoma and returned completely to normal after its removal. This response was independent of the plasma neuropeptide Y immunoreactivity manipulation and was correlated to increases in plasma noradrenaline (r = 0.638, P < 0.02) but not adrenaline levels. Manipulation-induced increases in plasma neuropeptide Y-immunoreactivity were associated with greater neuropeptide Y content in tumours (r = 0.508, P < 0.05) but neither plasma nor tumour levels of neuropeptide Y immunoreactivity were correlated to tumour mass. Plasma levels of neuropeptide Y immunoreactivity in the remaining 12 patients (41.4%, group II) remained unchanged throughout the experimental period, while levels of circulating catecholamine rose. In all, in spite of our attempt at complete adrenergic blockade, tumour manipulation elevated arterial blood pressure and these changes were significantly correlated to increases in levels of catecholamines in patients in both groups but also to plasma neuropeptide Y immunoreactivity in patients in group I. CONCLUSION: Pheochromocytomas exhibit different patterns of secretion. For about half of the patients either the secretion of neuropeptide Y is uncoupled from that of catecholamines or its secretion could be obscured by an increase in degradation of neuropeptide Y to inactive fragments undetectable by radioimmunoassay.

Hemorrheological indices, catecholamines, neuropeptide Y and serotonin in patients with essential hypertension.

Hemorrheological and humoral abnormalities and excessive platelet activity can predict the development of cardiovascular complications in patients with essential hypertension. A study was conducted to assess the influence of gender on these factors and the interrelations between changes in hemorrheology and the sympatho-adrenal system in 54 patients (18 women, 36 men) with essential hypertension (aged 39.6 +/- 9.7 years) and 25 healthy volunteers (10 women, 15 men; aged 36.0 +/- 7.2 years). A decrease in erythrocyte deformability (p < 0.01) was found in the hypertensive men compared with the hypertensive women. Hematocrit (p < 0.01), blood viscosity at the shear rates of 0.3 s-1 (p < 0.01) and 6 s-1 (p < 0.01), plasma viscosity (p < 0.01), erythrocyte aggregation (p < 0.01), and neuropeptide Y (p < 0.02) concentrations were higher in the hypertensive men than in the hypertensive women. A positive correlation between blood fibrinogen and serotonin was found in the pooled hypertensive group and in the hypertensive men (p < 0.01) and between blood viscosity (shear rate 6 s-1) and neuropeptide Y in the pooled hypertensive group (p < 0.01). Neuropeptide Y correlated with filtration time of 1 mL blood in the hypertensive men (p < 0.05) and in the pooled normotensive group (p < 0.01) and with beta-thromboglobulin in the hypertensive women (p < 0.001). A positive correlation was also found in the hypertensive men between erythrocyte and platelet aggregation (p < 0.01) and between beta-thromboglobulin and adrenaline (p < 0.01). Hemorrheological and humoral abnormalities are more pronounced in men than in women with essential hypertension and may contribute to the increased incidence of cardiovascular events in men.

Evaluation of plasma aldosterone to plasma renin activity ratio in patients with primary aldosteronism.

The plasma aldosterone to renin activity ratio (A/PRA) was assessed retrospectively in 103 patients with primary aldosteronism including 74 patients with surgically proven adrenal cortical adenoma (APA) and 29 patients with idiopathic adrenal cortical hyperplasia (IHA). The results were compared with those obtained in 31 patients with essential hypertension (EH) and 45 healthy normotensive controls. The upper limit of normal A/PRA ratio, as obtained in the controls was 17.8. This value was exceeded in 89% of patients with APA; postoperatively it decreased in 97% of the APA group, and returned to normal in 81%. In the IHA group the A/PRA was elevated in 70% of patients. The normal ratios in patients with primary aldosteronism were associated with unsuppressed plasma renin activity (PRA). Although the mean values of the A/PRA ratio differed significantly between the groups, complete separation was not obtained. The serum potassium level at time of testing did not influence the diagnostic value of the A/PRA ratio, although an inverse correlation between serum potassium and the A/PRA ratio was found in the patients with APA. This study supports the high sensitivity of the A/PRA ratio in diagnosis of primary aldosteronism, however, a single determination with a normal result may not be sufficient for exclusion of the disease.

[Evaluation of blood rheology indices in patients with pheochromocytoma]. / Ocena wskazników reologicznych krwi u chorych z pheochromocytoma.

Investigated group consisted of 28 patients (21 female and 7 male) with pheochromocytoma in mean age of 39.9 +/- 13 years, while control group comprised 25 healthy volunteers in mean age 36.0 +/- 7.2 years. Following parameters were determined: plasma and blood viscosity, erythrocyte and platelets aggregation, erythrocyte deformability, hematocrit, beta-thromboglobulin plasma concentration, plasma fibrinogen concentration, lipids concentration, noradrenaline, adrenaline, serotonin, neuropeptide Y plasma concentrations. Plasma fibrinogen and beta-thromboglobulin were increased in pheochromocytoma before surgery after pharmacological treatment and also after excision of the tumor. Whereas altered erythrocyte deformability before any treatment, only. Plasma neuropeptide Y concentration was higher in pheochromocytoma before surgery and after pharmacological treatment. There was no correlation between plasma catecholamines, plasma fibrinogen, beta-thromboglobulin, and erythrocyte deformability. Our results suggest that rheological abnormalities observed in patients with pheochromocytoma may contribute to vascular complications in this subjects. Sympathetic nervous system seems to influence indirectly observed rheological abnormalities.

Endothelin-1 and neuropeptide Y plasma concentrations in renal venous blood of hypertensive patients with unilateral renal artery stenosis.

The aim of the study was to investigate endothelin-1 (ET-1) and neuropeptide Y (NPY) plasma concentrations in renal venous blood of hypertensive patients with unilateral renal artery stenosis (URAS). The study was performed in 22 patients with URAS and 18 patients diagnosed as essentially hypertensive. In each subject renal arteriography and renal vein catheterisation was performed. Blood samples for ET-1, NPY and plasma renin activity (PRA) were withdrawn from renal veins and vena cava inferior, and for ET-1 and NPY from the aorta. Patients with URAS were divided in two subgroups according to the renal vein renin ratio. Both in nine patients with URAS and ratio > 1.5 and in 13 patients with URAS and ratio < 1.5, ET-1 and NPY plasma concentrations evaluated in renal venous blood of the ischaemic kidney were not different from those assessed in the contralateral side, in vena cava inferior and in the aorta. In essential hypertension, the mean ET-1 and NPY plasma concentrations of both renal veins were not different from the ET-1 and NPY plasma values assessed in renal vein of stenosed and contralateral side, vena cava and aorta of patients with URAS with and without activation of the renin system. Our study indicates that chronic ischaemia does not affect ET-1 and NPY plasma concentrations in renal venous blood of hypertensive URAS patients both with and without activation of the renin system.

Plasma neuropeptide Y and catecholamines in women and men with essential hypertension.

Neuropeptide-Y (NPY) is a peptide proposed to modulate the effect of the sympathetic nervous system on blood pressure control and contribute to the development of essential hypertension. To assess the possible influence of gender on its role, we evaluated plasma NPY, noradrenaline (NA) and adrenaline (A) concentrations in men and women with essential hypertension. No difference in NPY concentration was found between genders, but NPY concentration was elevated in both hypertensive men and women. NA levels were similar in all investigated hyper- and normotensives, while A was increased only in hypertensive men. These results suggest various patterns of sympatho-adrenal activity in gender subgroups of patients with essential hypertension.

Elevated plasma atrial natriuretic peptide concentrations in hypertensive patients with acute myocardial infarction.

BACKGROUND: Atrial natriuretic peptide (ANP) has been extensively studied in cardiovascular disorders in recent years. Particular attention has been paid to the role of ANP in the pathogenesis of hypertension and congestive heart failure and in the neurohormonal response to myocardial infarction. However, no published data are available on the significance of ANP in hypertensive patients with acute myocardial infarction. METHODS: We studied the relationship between plasma ANP concentration and systolic blood pressure, diastolic blood pressure, left atrial dimension, left ventricular diastolic dimension and left ventricular mass index in patients with essential hypertension in the acute phase of myocardial infarction. Plasma ANP concentrations were determined at 0, 4, 8, 16, 24, 48 and 72 h after admission in 40 patients with a first myocardial infarction (18 hypertensive patients, group 1; 22 normotensive patients, group 2). Left atrial dimension and left ventricular diastolic dimension were assessed echocardiographically within the first 48 h of acute myocardial infarction. RESULTS: Maximum and mean plasma ANP values at 0, 4, 8, 16, 24, 48, and 72 h as well as mean ANP concentrations within the 72 h period were higher in group 1 than in group 2 (P < 0.001). Plasma ANP concentration, left atrial dimension (r = 0.59) and left ventricular diastolic dimension (r = 0.56) were positively correlated in both groups. CONCLUSION: Acute myocardial infarction is characterized by a more pronounced rise in plasma ANP concentration in hypertensive patients than in those without a history of hypertension. Plasma ANP concentration correlates with left heart chamber sizes.

Neuropeptide Y and alpha-adrenoceptor interactions in patients with essential hypertension.

Neuropeptide Y (NPY) is a vasoconstrictor sympathetic cotransmitter and a modulator of adrenergic function whose role in hypertension is yet unknown. We studied the co-release of NPY and noradrenaline (NA) in patients with essential hypertension (13 females, 11 males, age 42 +/- 13 years) by measuring plasma levels of NPY-immunoreactivity (-ir, radioimmunoassay) and NA (radioenzymatic method) following administration of clonidine (CL 300 micrograms, p.o.). At rest, only NPY-ir levels significantly correlated with diastolic blood pressure (DBP, r = 0.42, p < 0.05). Three hours after CL, there were a decrease in mean arterial pressure and plasma NA (by 31 +/- 14 mmHG, p < 0.05 and 92 +/- 10 pg/ml, p < 0.01) but no change in NPY-ir levels. Patients were subsequently subdivided into groups with high (> or = 90 mmHg) or normal DBP (< or = 89 mmHg) and with or without elevated plasma NA levels (above or below 414 pg/ml, a normotensive mean +1 standard deviation). In hypertensives, but not in those with normal DBP, plasma NPY-ir correlated not only with DBP but also with systolic and mean blood pressure (r = 0.53 and r = 0.60, respectively) at rest. Hypertensives with "high" NA had significantly lower resting plasma NPY-ir levels than those with "low" NA (7.1 +/- 3.6 vs 14.7 +/- 6.0 fmol/ml, p < 0.05). In the former group, CL evoked the greatest fall in plasma NA, and also decreased NPY-ir levels by 50% (p < 0.05). Thus, patients with essential hypertension were found to display differential patterns of changes in sympathetic cotransmitters to clonidine. NPY may contribute to the increased blood pressure in hypertensives and together with NA, mediate hypotensive action of clonidine but only in the hyperadrenergic subgroup of hypertensives.

Postural stimulation test in patients with aldosterone producing adenomas.

OBJECTIVE: The purpose of this study was to evaluate the postural stimulation test before and after surgical treatment in patients with aldosterone-producing adenomas. DESIGN: The retrospective study was made on patients with aldosterone producing adenomas. PATIENTS: The postural stimulation test was analysed in 60 patients with surgically proven aldosterone producing adenoma and in 15 healthy volunteers. MEASUREMENTS: The postural stimulation test was based on measurements of plasma aldosterone, cortisol and renin activity (PRA) at 0800 h and at noon after 4 hours ambulation. RESULTS: The patients were divided into two groups according to the individual pattern of plasma aldosterone concentration following the postural test. Plasma aldosterone concentration decreased or did not change after 4 hours of standing in 42 patients (group 1, 70% of total) and increased in 18 patients (group 2, 30% of total). Mean plasma aldosterone was significantly higher in group 1 than in group 2 (1325 +/- 164 pmol/l (mean +/- SE) and 538 +/- 53 pmol/l, respectively). Mean plasma cortisol concentration after 4 hours of upright posture in both groups remained low (242 +/- 35 vs 401 +/- 63 nmol/l (group 1) and 317 +/- 46 vs 367 +/- 43 nmol/l (group 2)). Mean PRA in both groups was suppressed after 4 hours of upright posture (0.2 +/- 0.04 vs 0.2 +/- 0.04 pmol/l/s and 0.3 +/- 0.06 vs 0.1 +/- 0.02 pmol/l/s, respectively). CONCLUSION: Diverse changes in plasma aldosterone and cortisol found in response to the postural test may indicate pathogenetic heterogeneity amongst patients with aldosterone producing adenomas and should be considered during diagnosis of primary aldosteronism.

Elevated endothelin-1 plasma concentration in patients with essential hypertension.

BACKGROUND: Endothelin-1 (ET-1) may play an important role in the development and maintenance of hypertensive states. In patients with essential hypertension, ET-1 plasma concentration increases or remains unchanged. The aim of the present study was to investigate ET-1 plasma concentration in patients with mild-to-moderate essential hypertension and its interrelationship with catecholamines, neuropeptide Y and atrial natriuretic peptide (ANP). METHODS: The study included 37 patients (mean age 38.2 +/- 1.6 years) with mild-to-moderate essential hypertension. The control group consisted of 21 healthy volunteers (mean age 35.6 +/- 1.4 years). ET-1, neuropeptide Y and ANP were determined by radioimmunoassay methods and catecholamine plasma concentration was determined radioenzymatically. RESULTS: Our study shows that plasma ET-1 and neuropeptide Y levels are elevated in patients with essential hypertension compared with a control group. No correlation was found in either of the groups between plasma ET-1 level and plasma neuropeptide Y, catecholamine or ANP concentrations. CONCLUSION: Our results suggest that ET-1 is relevant in the development and maintenance of elevated blood pressure.

[Primary prostaglandins PGE2, PGF2, prostacyclin and thromboxane in patients with myocardial infarction]. / Prostaglandyny pierwotne PGE2, PGF2 alpha, oraz prostacyklina i tromboksan u chorych z zawalem serca.

In 47 patients with acute myocardial infarction and in 17 healthy volunteers blood concentration and urinary excretion of PGE2, PGF2 alpha, 6-keto-PGF1 alpha--hydrolysis product of prostacyclin--and TXB2 were determined using RIA. Myocardial infarction patients were found to have significantly higher blood level and urinary excretion of 6-keto-PGF1 alpha, higher blood level of PGF2 and higher urinary excretion of TXB2 than controls, PGE2 urinary excretion was significantly lower. Increased excretion of 6-keto-PGF1 alpha was observed in patients with ventricular arrhythmias. Excretion of all determined prostaglandins was increased in patients with myocardial infarction complicated by atrioventricular block as compared to the other patients. The results suggest, that increase of prostacyclin synthesis in the acute phase of myocardial infarction may provide protection mechanism against heart muscle damage and improve coronary blood flow.

Plasma atrial natriuretic peptide (ANP) concentration in patients with pheochromocytoma.

The interaction between catecholamines (CA) and ANP is not clearly established. The effects of excess endogenous CA on ANP secretion can be investigated in patients with pheochromocytoma. We studied 27 patients with surgically and histologically proven pheochromocytoma (P) aged 19-70 years. In 16 of these patients plasma ANP study was repeated after surgical removal of the tumour. The control group (C) consisted of 20 healthy volunteers aged 21-48 years. Moreover, 42 patients with uncomplicated mild to moderate essential hypertension (EH) aged 18-48 years were also studied. In P higher plasma ANP concentration versus C, EH was found (51.9 +/- 8.1; 25.5 +/- 1.5; 19.3 +/- 1.5 fmol/ml, respectively). In 16 patients with P, increased plasma ANP level (mean 63.3 +/- 12.6 fmol/ml) declined after surgical removal of the tumour (mean 22.4 +/- 2.9 fmol/ml). In the P patients no relationship was found between plasma ANP and hormonal patterns of the tumour or between plasma ANP and plasma catecholamines, whereas significant positive correlations between plasma ANP and both systolic and diastolic blood pressure and heart rate were demonstrated. These results suggest that excess CA produced by the chromaffin tumour induce ANP secretion via stimulation of adrenergic receptors. However, influence of the haemodynamic changes evoked by CA cannot be excluded. It is suggested that increased secretion of ANP may be of some importance in maintaining blood pressure homeostasis in patients with pheochromocytoma.

[Effect of hemodialysis on the level of serum digoxin-like substance and sodium-potassium pump activity in erythrocytes from patients with chronic renal failure]. / Wplyw hemodializy na stezenie substancji digoksynopodobnej w surowicy krwi i aktywnosc pompy sodowo-potasowej w erytrocytach chorych z przewlekla niewydolnoscia nerek.

Digoxin-like immunoreactivity (DLS) and erythrocyte sodium-potassium pump (PSP) activity were measured in a group of 16 patients with chronic renal failure (CRF) before and just after haemodialysis and in a group of 9 healthy persons. Before haemodialysis DLS was present in the blood of most CRF patients, at the mean concentration of 0,14 +/- 0,13 micrograms/l. After haemodialysis DLS concentration decreased to 0,09 +/- 0,09 microgram/l (p less than 0,01). In the control group blood DLS concentration was nondetectable. In the CRF group PSP activity was higher before than after haemodialysis (p less than 0,01; 12,1 +/- 1,8 and 7,6 +/- 1,4 muMol Pi/h/g Hb. PSP activity in the control groups was 10,3 +/- 1,9 muMol Pi/h/g Hb). In the CRF group PSP activity was higher before haemodialysis (p less than 0,05) and lower after haemodialysis (p less than 0.01) than in the control group. Our results confirmed the presence of DLS in the blood of the majority of CRF patients. DLS concentration decreased after haemodialysis but we did not found any parallel increase in PSP activity in these patients. These results did not confirm the hypothesis that DLS might inhibit PSP activity in red blood cells from CRF patients.

[Blood pressure in patients after unilateral adrenalectomy for aldosterone producing adrenal adenoma]. / Cisnienie tetnicze u chorych po jednostronnej adrenalektomii z powodu gruczolaka kory nadnerczy wytwarzajacego aldosteron.

Forty five patients (35 women and 10 men) who underwent adrenalectomy for aldosterone-producing adrenal adenoma were followed up for 5.7 +/- 4.7 years (1-17 years). Stable normalization of blood pressure was noted in 27 (60%) patients. In 16 patients the primary hypertension and in 1 patient the second adrenal adenoma were diagnosed after surgery. Statistically significant decrease in daily excretion of adrenaline and noradrenaline with the urine, reduced adrenaline/noradrenaline ratio and reduced catecholamines and their metabolites ratio were noted in the operated patients in comparison to healthy volunteers indicating catecholamines metabolism disorders. Surgical treatment of adrenal adenoma besides normalization of blood pressure diminishes biochemical abnormalities. Development of the primary blood hypertension may be expected in some patients.

[Blood level of free serotonin, catecholamines and the renin-angiotensin-aldosterone system in patients with primary hypertension]. / Substancja digoksynopodobna we krwi a cisnienie tetnicze u dializowanych chorych na przewlekla niewydolnosc nerek.

Two subgroups of patients were selected out of those dialysed for chronic renal failure. Group A included patients without arterial hypertension before dialysis, and group B patients with arterial hypertension before dialysis. Blood endogenous digoxin-like substance (DLS) has been assayed. Its blood levels were not increased in hypertensive patients either before or after dialysis. No correlation was found between DLS and mean arterial pressure in the whole group of patients with chronic renal failure. The obtained results do not suggest that arterial blood pressure in patients with chronic renal failure is related to the presence of DLS in the blood.

Platelet activity, prostacycline metabolite, plasma lipids and sympathoadrenal activity in patients with borderline hypertension and a positive family history of hypertension.

The study included 30 patients with borderline essential hypertension (HPT) (21 with a positive family history of hypertension, mean age 24.6 years, 9 with a negative family history, mean age 27.2 years) and 10 normotensive controls (mean age 27.5 years). In all of them 24-hour urinary noradrenaline (NA) and adrenaline (A) excretion was assayed. Blood levels of NA, A and dopamine, the prostacycline metabolite 6-keto-PGF1 alpha, beta-thromboglobulin, cholesterol, triglycerides and HDL cholesterol were measured, LDL cholesterol was calculated according to the Friedewald equation. Besides, lecithin cholesterol acyltransferase activity was assayed. Patients with HPT and a positive family history had elevated sympathetic and platelet activity and diminished 6-keto-PGF1 alpha blood levels. Their HDL cholesterol level was significantly lower than that of healthy controls. In patients with HPT and a positive family history of HPT the atherogenic index (total cholesterol to HDL cholesterol ratio) was highest, but did not differ significantly from that in other groups. The assessment of the examined humoral factors indicates that patients with borderline HPT with genetic predisposition to high blood pressure have a humoral profile different from that of patients without genetic predisposition. These findings suggest the importance of genetic factors in the development of essential HPT.

[Effects of 4-hour erect posture and furosemide on the blood level of atrial natriuretic peptide in patients with primary arterial hypertension]. / Wplyw 4-godzinnej czynnej pionizacji i furosemidu na stezenie przedsionkowego peptydu natriuretycznego we krwi u chorych z nadcisnieniem tetniczym pierwotnym.

The arterial pressure, the pulse frequency, the concentration of arterial natriuretic peptide (ANP), the aldosterone++ concentration and the plasma renin activity were determined in patients with primary hypertension after administration of furosemide in conditions of active assuming of erect position. The ANP concentration was lowered in that conditions both in the patients and in healthy subjects.