K.H. Rahn

Different effects of hypertension, atherosclerosis and hyperlipidaemia on arterial distensibility.

Objective To investigate the different effects of hypertension, hyperlipidaemia and atherosclerosis on the visco-elastic properties of large arteries. Design Vessel wall properties were determined in patients who had been subjected for the first time to coronary arteriography. Normotensive patients with no coronary disease (n = 15), one-vessel disease (n = 15) or two- or three-vessel disease (n = 15), 15 treated hypertensive patients (mean ± SEM duration of hypertension 9.6 ± 1.7 years) with no coronary disease and normocholesterolaemia and 15 healthy controls were matched for blood pressure, age and sex. Methods Arterial distension of the common carotid artery was determined by using a multigate Doppler system. The blood pressure curve was recorded by finger plethysmography. Results The end-diastolic diameter was significantly higher in the hypertensives (P < 0.05) but not significantly different in the normotensives compared with the controls. Arterial distensibility was significantly lower in the hypertensive group [(13.3 ± 0.8) x 10-3/kpa] than in the controls [(19.1 ± 1.5) x 10-3/kP; P < 0.01), in the group with no coronary disease [(18.8 ± 1.3) x 10-3/kPa; P < 0.01] and in those with one-vessel disease [(17.7 ± 1.4) x 10-3/kPa; P < 0.05]. Arterial distensibility was not significantly lower in the hypertensives than in the group with two- or three-vessel disease [(15.0 ± 1.0) x 10-3/kPa; NS). No significant correlation was found between cholesterol or lipoprotein(a) levels and arterial distensibility in the normotensive patients. Conclusions Hypertension is the predominant factor affecting the visco-elastic properties of large arteries. Arterial compliance is significantly altered only in extensive atherosclerosis.

Circadian Blood Pressure Variations in Endocrine Disorders

Circadian rhythm of blood pressure and of heart rate was studied in patients with hyperthyroidism (n = 10), pheochromocytoma (n = 8), primary hyperaldosteronism (n = 7), and in a control group of essential hypertensive patients (n = 18) and of normotensive healthy subjects (n = 11). 24-hour blood pressure was monitored non-invasively using SpaceLabs (SL 90207) with 8-min intervals in the daytime (8 a.m. to 10 p.m.) and 30-min intervals during night-time (10 p.m. to 8 a.m.). To characterize circadian blood pressure rhythm the difference between the mean blood pressure during daytime and that during night-time was calculated. In patients with hyperthyroidism the day-night difference of the systolic and diastolic blood pressure and of the heart rate was significantly reduced when compared to the normotensive control group (p < 0.05). The day-night difference of the systolic and diastolic blood pressure was significantly lower in the group with pheochromocytoma and hyperthyroidism than in the essential hypertensive controls (p < 0.05); the day-night difference of the heart rate was similar. In the patients with primary hyperaldosteronism the day-night differences of the systolic and diastolic blood pressure and of the heart rate was similar to those in essential hypertensive controls. We conclude that endocrine disorders affecting sympathetic activity like pheochromocytoma or hyperthyroidism influence the circadian blood pressure rhythm, whereas the renin-aldosterone-system has no major impact on the diurnal blood pressure variation. The results therefore support the hypothesis that circadian blood pressure variation is mainly mediated by a modulation of the sympathetic tone.

Plasma and Membrane Ca2+ and Mg2+ Concentrations in Normal Pregnancy and in Preeclampsia

Objective: Changes in intracellular Ca²⁺ and Mg²⁺ concentrations seem to be involved in the pathogenesis of preeclampsia, whereas the role of cell membranes has not been studied in detail yet. To investigate the changes in Ca²⁺ and Mg²⁺ metabolism in normal pregnancy and preeclampsia, plasma and membrane Ca²⁺ and Mg²⁺ concentrations were determined in a clinical study as compared to healthy subjects. Study Design: 25 healthy female subjects, 22 untreated healthy pregnant and 20 preeclamptic women were investigated. In each patient, plasma and membrane Ca²⁺ and Mg²⁺ content were measured. Ca²⁺ and Mg²⁺ concentrations were measured by atomic absorption spectroscopy. Erythrocyte membranes were chosen for membranous Ca²⁺ and Mg²⁺ determination. Results: Plasma Mg²⁺ concentrations were significantly lowered in the healthy pregnant group and the preeclamptic group as compared to contols (p < 0.0001). In erythrocyte membranes, Mg²⁺ content was found significantly decreased in the preeclamptic women as compared to healthy subjects (p < 0.001). In plasma Ca²⁺ concentrations there was a significant decrease in the preeclamptic group as compared to controls or healthy pregnant women (p < 0.05). Membranous Ca²⁺ content was significantly increased in the preeclamptic group versus controls or healthy pregnant women (p < 0.001). Conclusion: Lowered plasma and membrane Mg²⁺ concentrations in preeclampsia may contribute to the development of hypertension in pregnancy. Additionally, a disturbed Ca²⁺ homeostasis is observed in preeclampsia.

Decreased cellular Mg2+ concentrations in a subgroup of hypertensives--cell models for the pathogenesis of primary hypertension.

A new method to determine total Mg2+ content in lymphocytes was developed, offering advantages for routine measurements as compared to fluorescence methods. Intracellular Mg2+ measurements were performed in lymphocytes of 18 untreated normotensive and 19 untreated essential hypertensive patients. Mg2+ content was referred to lymphocytic protein, which was determined according to Bradford’s method. Mg2+ measurements were performed by atomic absorption spectroscopy using a Video 12 apparatus from Thermo Electron Instrumentation Laboratory, Andover, MA, USA. The results show that in patients with essential hypertension, total intralymphocytic Mg2+ content is significantly lower (0.07 ± 0.05 mmol/g lymphocytic protein, mean ± s.d.) as compared to controls (0.11 ± 0.04 mmol/g lymphocytic protein, mean ± s.d., P <0.05). free intracellular mg2+ content was measured in lymphocytes by the fluorescent indicator mag-fura-II, showing no significant difference in normotensives and hypertensives (0.30 ± 0.16 vs 0.38 ± 0.17 mmol/l). In platelets free intracellular Mg2+ concentrations were not found of significant difference in normotensive and hypertensive patients (0.52 ± 0.23 vs 0.47 ± 0.27 mmol/l) using mag-fura-II. In plasma Mg2+ concentrations there was no significant difference in the normotensive and hypertensive group (0.92 ± 0.07 vs 0.88 to 0.07 mmol/l). There was no correlation between plasma, free or total cellular magnesium concentrations in each group. Furthermore this method also seems suitable for routine measurements of total intracellular Mg2+ concentrations in even larger groups of patients in comparison with fluorescent indicator measurements like mag-fura-II. Lowered total intracellular Mg2+ concentrations in a subgroup of primary hypertension may contribute to the development of this disorder, perhaps due to different buffering systems.

Studies on cardiac sympathovagal balance and large artery distensibility in patients with untreated essential hypertension

Background: Power spectral analysis of heart rate variability and arterial distensibility are non-invasive measures of cardiac autonomic modulation and mechanical vessel wall properties, respectively. The aim of the present study was to assess cardiac sympathovagal balance, carotid and brachial artery distensibility and a possible relation between these parameters in mildly hypertensive patients as compared to normotensive controls. Methods: Total power (TP, 0.01 to 0.5 Hz) and spectral components (low frequency 0.04–0.15 Hz, mainly sympathetic cardiac modulation; high frequency 0.15–0.4 Hz, mainly vagal cardiac modulation) and cardiac sympathovagal balance (LF/LH ratio) of short term heart rate variability (ECG-recording) were calculated in 15 untreated essential hypertensive patients (HYP) and 15 age- and sex-matched healthy controls (CON). Brachial and carotid artery distensibility coefficient (DC) was measured with a multigate doppler system (echo-tracking). Results: TP (ms2 × 10−3) (11.2 ± 0.8 vs 13.6 ± 0.9, P < 0.03), lf/hf ratio (1.07 ± 0.08 vs 0.75 ± 0.07, P < 0.01) and hf (ms2 × 10−3/%) (0.7 ± 0.1/49 ± 2 vs 1.3 ± 0.2/58 ± 2, P < 0.01/P < 0.01) were significantly reduced in hyp compared to con subjects. lf (ms2 × 10−3/%) was 0.7 ± 0.1/50 ± 2 vs 0.9 ± 0.1/41 ± 2, P = 0.16/P < 0.01. carotid artery dc (15 ± 2 vs 26 ± 2 P < 0.001) and brachial artery dc (4.7 ± 0.6 vs 9 ± 1.0, P < 0.001) were significantly reduced in hyp. there was a significant correlation between carotid dc and lf/hf (rho = −0.41, P < 0.03). Conclusion: The data shows reduced heart rate variability and altered cardiac sympathovagal balance as well as impaired arterial distensibility in untreated mildly hypertensive patients. The relative increase in sympathetic modulation and decreased carotid distensibility appear to be related.

Alterations of plasma calcium and intracellular and membrane calcium in erythrocytes of patients with pre-eclampsia.

Background: Changes in plasma and intracellular calcium levels have been suggested in the pathogenesis of pre-eclampsia, however, membrane calcium content has not been studied so far. We compared intracellular and membrane calcium concentrations in erythrocytes of women with pre-eclampsia, healthy pregnant woman and controls to determine a possible alteration of membrane calcium in pre-eclampsia.Subjects and methods: Eighteen untreated, healthy pregnant woman and 16 pregnant nulliparous women with manifest pre-eclampsia were included, 25 healthy, age-matched woman served as controls. Atomic absorption spectroscopy was used for measurement of intracellular and membrane calcium content in erythrocytes and plasmalemmal preparations.Results: Plasma Ca++ concentrations were significantly lower in pre-eclamptic women (1.96 ± 0.15 mmol/l, P < 0.01, mean ± s.e.m.) compared to healthy controls (2.43 ± 0.14 mmol/l) or women with uncomplicated pregnancies (2.20 ± 0.10 mmol/l). intracellular ca++ concentrations were not different between groups, however, membrane Ca++ content was significantly increased in the pre-eclamptic patients (1.23 ± 0.36 μmol/g membrane protein, P < 0.01) compared to control subjects (0.83 ± 0.16 μmol/g) and healthy pregnant women (0.77 ± 0.13 μmol/g).Conclusion: Membrane calcium content is significantly increased in pre-eclamptic women despite low plasma Ca++ concentrations. This finding suggests an altered membrane ion transport and may be of importance for the pathogenesis of pre-eclampsia.

A longitudinal study of vessel wall properties in normotensive and hypertensive renal transplant recipients.

The mechanisms responsible for reduced arterial distensibility in renal transplant recipients remain to be evaluated. The present longitudinal study was aimed to evaluate the effect of hypertension on the evolution of vessel wall properties in renal transplant recipients. The mechanical properties of the common carotid artery were determined in 24 normotensive and 24 treated hypertensive renal transplant recipients 6–12 weeks after transplantation. The measurements were repeated after 2 years. Arterial distension was determined by using a multigate pulsed Doppler system, blood pressure (BP) was measured by a mercury sphygmomanometer. BP was 127 ± 3/80 ± 2 mm Hg at entry and 133 ± 3/82 ± 2 mm Hg after 2 years in the normotensive group, 146 ± 4/90 ± 3 mm Hg at entry and 145 ± 3/87 ± 2 mm Hg after 2 years in the hypertensive group (P < 0.01, normotensives vs hypertensives). The distensibility coefficient (DC) decreased significantly after 2 years in the hypertensive group (DC 18.3 ± 1.3 10−3/kPa before, 15.1 ± 1.2 10−3/kPa after 2 years, P < 0.05) whereas no significant change was observed in the normotensive group (dc 19.0 ± 1.4 10−3/kPa before, DC 17.8 ± 1.3 10−3/kPa after 2 years, NS). There was a significant correlation between the change of the distensibility coefficient after 2 years and mean arterial pressure (n = 48, r = 0.42, P < 0.01). the results show that the decrease of arterial distensibility after 2 years is accelerated in hypertensive renal transplant recipients despite effective anti-hypertensive treatment. since bp levels were not different at entry into the study and after 2 years, differences in distending pressure along cannot explain the more pronounced decrease of arterial distensibility over time in hypertensive renal transplant recipients.

Studies on diurnal blood pressure variation in kidney diseases associated with excessive salt and water retention

Salt and water retention, a cardinal feature of nephrotic syndrome, was suggested to be an important factor leading to reduced diurnal blood pressure (BP) variation in renoparenchymal disease. Twenty-four hour BP (SpaceLabs SL 90207), 24-h urine excretion of catecholamines, plasma renin activity and plasma aldosterone concentration were therefore determined in 10 nephrotic patients with normal serum creatinine levels (group A, serum creatinine 1.0 ± 0.2 mg/dl), in 10 nephrotic patients with increased serum creatinine levels (group B, serum creatinine 2.4 ± 0.9 mg/dl) and in 20 controls matched in respect of age and BP. To study the direct influence of fluid volume overload, diurnal BP variation was determined before and after volume depletion by ultrafiltration in 10 patients with end-stage renal failure. Diurnal BP variation was characterised by the difference of mean BP during daytime (10 pm to 8 am) and night-time (8 am to 10 pm). In group A, the systolic and diastolic day–night difference was not changed when compared with the controls (NS). In contrast, in group B the day–night difference was significantly lower than in the controls (P < 0.01). twenty-four hour urine catecholamine excretion and plasma aldosterone were comparable between the study groups. plasma renin activity, however, was significantly increased in group a (P < 0.05). nocturnal bp drop was not related to plasma renin activity in the nephrotic patients. the blunted diurnal blood pressure variation in end-stage renal failure was not influenced by ultrafiltration. the study demonstrates that the blunted diurnal bp variation in kidney disease is unaffected by marked changes in total exchangeable sodium and fluid volume, but is sensitive to changes in glomerular filtration rate.

Plasma and membrane Ca++ and Mg++ concentrations in normal pregnancy and in preeclampsia.

OBJECTIVE Changes in intracellular Ca2+ and Mg2+ concentrations seem to be involved in the pathogenesis of preeclampsia, whereas the role of cell membranes has not been studied in detail yet. To investigate the changes in Ca2+ and Mg2+ metabolism in normal pregnancy and preeclampsia, plasma and membrane Ca2+ and Mg2+ concentrations were determined in a clinical study as compared to healthy subjects. STUDY DESIGN 25 healthy female subjects, 22 untreated healthy pregnant and 20 preeclamptic women were investigated. In each patient, plasma and membrane Ca2+ and Mg2+ content were measured. Ca2+ and Mg2+ concentrations were measured by atomic absorption spectroscopy. Erythrocyte membranes were chosen for membranous Ca2+ and Mg2+ determination. RESULTS Plasma Mg2+ concentrations were significantly lowered in the healthy pregnant group and the preeclamptic group as compared to controls (p < 0.0001). In erythrocyte membranes, Mg2+ content was found significantly decreased in the preeclamptic women as compared to healthy subjects (p < 0.001). In plasma Ca2+ concentrations there was a significant decrease in the preeclamptic group as compared to controls or healthy pregnant women (p < 0.05). Membranous Ca2+ content was significantly increased in the preeclamptic group versus controls or healthy pregnant women (p < 0.001). CONCLUSION Lowered plasma and membrane Mg2+ concentrations in preeclampsia may contribute to the development of hypertension in pregnancy. Additionally, a disturbed Ca2+ homeostasis is observed in preeclampsia.

Renal function in treated and untreated hypertension

There is now increasing evidence that essential hypertension is a serious risk factor for renal insufficiency. It has been known for many years that malignant essential hypertension rapidly causes deterioration of kidney function. This can be prevented by treatment with anti-hypertensive drugs. Mild-to-moderate essential hypertension causes significant renal function impairment only after a number of years. There are now data suggesting that the decline of renal function caused by mild-to-moderate essential hypertension can be prevented by anti-hypertensive treatment. In recent years, it has been demonstrated that anti-hypertensive drugs have a beneficial effect on the progression of renal insufficiency in patients with diabetic nephropathy and in chronic glomerulonephritis. In these situations, ACE inhibitors appear to be superior to other classes of anti-hypertensive drugs.