Nitrendipine treatment in so-called therapy-resistant arterial hypertension; effect as monotherapy and in combination with propranolol on blood pressure, heart rate, other hemodynamic parameters, plasma renin activity, and catecholamines.

Twenty-three patients [mean age 49.7 +/- 5.6 years (WHO II-III)] with severe hypertension and not responding to previous drug treatment were included in the study to evaluate the effect of nitrendipine (NTP) as monotherapy and also in combination with propranolol (PRO). After a control period of 10 days, NTP was started with 20 mg twice a day and titrated to the maximal dosage of 2 X 40 mg/day. After 1 week of NTP treatment, PRO was added in increasing dosage to a maximal 2 X 100 mg/day. NTP lowered systolic and diastolic blood pressure (BP) significantly (supine BP from 182/119 +/- 19/9 to 157/98 +/- 16/9 mm Hg). After combination with PRO, systolic BP was decreased additionally (supine BP from 157/98 +/- 16/9 to 150/97 +/- 19/9 mm Hg). Plasma norepinephrine (NE) was increased by NTP (from 1.82 +/- 0.78 to 2.38 +/- 1.08 nmol/l, p less than 0.01) and remained elevated during PRO treatment (2.76 +/- 1.10 nmol/l). Plasma renin activity (PRA) showed no significant changes by NTP. Additional effect of PRO on BP correlated significantly with NE and PRA after the NTP period. Plasma epinephrine and dopamine beta-hydroxylase remained unchanged. NTP decreased systemic resistance, calculated from isotope dilution technique (p less than 0.05); after combination with PRO no additional significant changes were registered. Nitrendipine is an effective alternative in so-called therapy-resistant hypertension.

[The blood pressure-regulating role of the renin-angiotensin system in essential hypertension before and after emotional stress]. / Zur blutdruckregulativen Rolle des Renin-Angiotensin-Systems bei essentiellen Hypertonikern vor und nach psychoemotionalem Stress.

The aim of the study was to prove the correlations between systolic and diastolic blood pressure (BP), heart rate (HR) and plasma renin activity (PRA) under mental arithmetic stress without and with beta-blockade. 22 male hypertensive patients (aged 19-39 years) were examined, divided into a group treated with d, 1-propranolol (Obsidan) and a control group receiving placebo. Under arithmetic stress the kinetics of systolic BP showed no differences even after beta-blockade. In contrast, the increases of HR and PRA before, during and after mental arithmetic were either significantly reduced (HR) or completely blocked (PRA) under beta-blockade. However, these suppressions of HR and PRA did not prevent the stress-induced elevations of systolic and diastolic BP under beta-blockade.

[Saralasin test in the differential diagnosis of essential and renal hypertension]. / Der Saralasintest in der Differentialdiagnostik essentieller und renaler Hypertonien.

In a multicentric prospective study should be tested clinically the effectiveness and the tolerance of an angiotensin-II-antagonist (Saralasin-IWF) developed by the Institut für Wirkstofforschung der Akademie der Wissenschaften, its position in the differential-diagnostic step programme of the arterial hypertension should be analysed and with it should be performed pathogenetic investigations for hypertension after kidney transplantation. Taking into consideration international studies our results confirm that the Saralasin test, taking into account strongly standardized methodical prerequisites, is suited to objectify a participation of the RAAS in the hypertension pathogenesis, without, however, thus making an absolutely reliable evidence concerning the etiology of hypertension. The Saralasin test may represent an important diagnostic criterion for an optimization of the therapy of "volume-resistant" hypertension under the conditions of haemodialysis and in connection with selective renin determinations it possesses a high value in the screening diagnostics of the arterial stenosis after allogenic kidney transplantation.

[Experimental studies of the pathogenesis of hypertension immediately following kidney transplantation]. / Experimentelle Untersuchungen zur Pathogenese der unmittelbar nach Nierentransplantation auftretenden Hypertonie.

To investigate pathomechanisms of the hypertension originating immediately after kidney transplantation, acute model studies were performed on binephrectomised hypertensive dogs receiving a cold-stored autograft. Comparative determinations of freely circulating renin-angiotensin und catecholamines were made after transplantation of canine and human kidneys, showing a corresponding post-anastomotic increase in plasma levels. For estimation of the vascular contractile response to the high plasma transmitter concentrations, antagonists having different pharmacological characteristics were infused in the dogs. It was found that immediately after transplantation the kidney's vasopressor system had only a moderate impact on increase in systemic and renal resistance. Using inhibitors of central sympathetic activities, also a moderate decline in blood pressure was observed, but it unfortunately led to a decrease in renal blood flow and filtration. The direct vasodilatatoric stimulation of vascular smooth muscle had no hemodynamic effects. However, the peripheral alpha-adrenergic blockade induced a marked decrease in blood pressure as well as an almost complete normalization of the elevated arteriolar tone of the graft associated with an increase in glomerular filtration. The suppression of vascular alpha-adrenergic stimulation was likewise attainable by inhibition of the neuro-muscular transmission due to calcium channel blockade. The results suggest that sympathetic vasoconstriction plays the major role in producing this type of posttransplant hypertension.

[Changes in blood pressure and serum lipids with fish diets in patients with mild essential hypertension]. / Anderungen von Blutdruck und Serumlipiden unter Fischdiäten bei Patienten mit milder essentieller Hypertonie.

14 male patients with moderate essential hypertension were treated in the cross-comparison with a mackerel and herring diet, respectively, for two weeks. The mackerel diet contained double as much eicosapentaenic (EPA) and docosahexaenic acid (DHA) as the herring diet which served as control. In the serum triglycerides particularly DHS, in the cholesterol esters above all EPA were enriched. In the phospholipids the increase of the two fatty acids was approximately the same. At the end of the mackerel period the serum triglycerides, the total and LDL-cholesterol, the activity of the lecithin-cholesterol-acyl-transferase (CALT) and the serum sodium were significantly decreased. On the other hand, the HDL-cholesterol and the uric acid in the serum significantly increased. Under influence of the herring diet the parameters mentioned appeared only slightly changed. After the mackerel diet also a significantly lower systolic blood pressure was found. The systolic and diastolic blood pressure during a standardized psychophysiological stress test was more diminished at the end of the mackerel period than after the herring diet. The plasma renin activity (PRA) was increased after the mackerel diet. Its increase under the stress test could no more be proved at the end of the mackerel diet. In similar way the stress-conditioned increase of thromboxane B2 could no more be observe both after mackerel and after herring diet. When the results should confirm themselves in long-term studies, a mackerel diet in practicable dosage can be recommended as non-medicamentous treatment of moderate hypertension.

Blood pressure- and lipid-lowering effect of mackerel and herring diet in patients with mild essential hypertension.

Fourteen male patients with mild essential hypertension were put on a mackerel and herring diet within a prescribed isocaloric regimen in a cross-over design for 2 weeks. After mackerel diet eicosapentaenoic acid (EPA-C20:5, n-3) appeared more in cholesterol esters (1.7-11.0%), whereas docosahexaenoic acid (DHA-C22:6, n-3) was predominantly incorporated into serum triglycerides (1.0-8.3%). After herring diet, which contained half as much EPA and DHA, their increase was of minor degree. After mackerel diet serum triglycerides, total cholesterol, LDL cholesterol and lecithin cholesterol acyl transferase (LCAT) activity were significantly decreased (by 28%, 9%, 14% and 14%, respectively), returning to the initial levels 3 months later. On the contrary, HDL cholesterol appeared significantly increased (by 12%). After herring diet the differences were not significant. Serum sodium was significantly lower (by 2%) at the end of the mackerel diet as compared to the initial values. On the other hand, uric acid in serum appeared transiently increased (by 24%) at the end of both dietary periods. A significant decrease (by 8%) in casual systolic blood pressure, measured in recumbent position, could be observed only at the end of the mackerel period. Moreover, the level of systolic and diastolic blood pressure before and during a standardized psychophysiological stress test was significantly lower after mackerel diet. Nevertheless, the increments after stress were similar. Plasma renin activity was increased (by 64%) after mackerel diet.(ABSTRACT TRUNCATED AT 250 WORDS)

[The antihypertensive effect of saralasin in rabbits with neurogenic interoreceptive hypertension]. / Der antihypertensive Saralasin-Effekt bei Kaninchen mit neurogen-interorezeptiver Hypertonie.

The renal nerve activity plays an essential role in the stimulation of plasma renin activity (PRA), which may be involved in the pathomechanism of neurogenic hypertension after sino-aortic denervation (SAD). Therefore, studies were conducted on unanesthetized rabbits (10 animals; 3-4 kg) after bilateral carotid sinus denervation plus section of cervical aortic nerves and the patterns of blood pressure (BP), heart rate (HR), and PRA were measured after a single injection-dosis of Saralasin (i.v., 10 micrograms/kg). After SAD the BP increased rapidly to 190 mm Hg within one week and remained at this high level (190-220 mm Hg) throughout the whole experiment (120 weeks). No change in BP of control rabbits (100-110 mm Hg) could be observed. Two weeks after SAD, the PRA showed a short elevation (approx. 25 ng) which subsequently returned to the levels of control rabbits (approx. 19 ng). Only in hypertensive rabbits Saralasin produced a short decrease of BP during both the initial and the whole chronic phases of hypertension, which was associated with a larger decrease of HR (1st to 5th min). Surprisingly, Saralasin induced a drop of HR also in the control rabbits. Our results suggest that also the normalized renin-angiotensin system is involved in the pathomechanism of sympathetic induced SAD-hypertension and probable permanently support the chronic state of hypertension by a relative "reninism".

Evidence of decreased plasma substance P levels in human essential hypertension and influence of prazosin treatment.

Patients with essential hypertension (n = 45) had significantly lower substance P plasma levels (13.6 +/- 2.30 pg/ml) in comparison with a group of 24 normotensive subjects (45.4 +/- 7.18 pg/ml) analyzed by radioimmunoassay. Prazosin treatment for 2 weeks with 4.5 mg/day enhanced the substance P plasma level depending on its antihypertensive effect. Norepinephrine concentration in plasma was also elevated by prazosin. Dipeptidylpeptidase IV, dopamine-beta-hydroxylase and plasma renin activity were not changed significantly. The results indicate the participation of substance P in pathophysiological processes of human essential hypertension.

[Effect of angiotensin II on the conditional relfex response patterns of neurotic albino rats]. / Uber die Wirkung von Angiotensin II auf bedingt-reflektorische Reaktionsmuster neurotischer Albinoratten

The effect of one single dose of 10 ng Angiotensin II/kg body weight upon affirmed conditional-reflectory response patterns (two-dimensional conditional-reflectory decision process and periodicities of conditional-reflectory processes) was studied in 50 male albino rats in which a neutrotically induced hypertensive blood pressure regulation had been elicited by stress exposure for 135 days. Contrary to healthy animals in which Angiotensin II was demonstrated to act in a biphasic manner, the neurotic animals revealed a monophasic action manifesting itself by a generalized centralnervous excitation. It was noticed, furthermore, that the information processing and regulatory processes of the CNS are considerably disturbed. The chronically hypertensive systolic blood pressure values of neurotic animals, like in healthy ones, show a brief, transient rise immediately following administration of Angiotensin II. These results are not only another proof of a neurotropic component of Angiotensin II action, but they show also that this action allows one to judge the state of disturbed nervous functions. The correlation of the neurotropic effect of Angiotensin II with pathogenetic mechanisms of experimental neurotically induced hypertension is discussed.