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Background: It can be assumed that endothelin (ET) the hitherto most powerful known vasoconstricting agent participates in the regulation of BP. The objective of this investigation was to compare ET plasma concentrations in different stages and types of arterial hypertension and to assess its possible participation in a rise of the BP., Methods and Results: The authors assessed plasma concentration of ET1,2, using the RIA method, in 27 normotensive controls, 30 normotensive subjects with a family-history of hypertension, 21 patients with mild essential hypertension (EH), eight severe cases of EH and 27 patients with chronic renal failure who were in a regular dialyzation programe, incl. 13 treated on account of hypertension; in 14 the BP was within the normal range. The ET examination was supplemented by RIA assessment of the plasma renin activity (PRA). The authors recorded significantly higher ET concentrations as compared with controls (14.0 +/- 0.9 fmol/ml) in normotensive subjects from hypertensive families (18.1 +/- 1.2 fmol/ml), severe EH (26.1 +/- 3.2 fmol/l). Hypertensive patients with chronic renal failure (CHRS) had also higher ET levels (26.5 +/- 2.8 fmol/l). Patients with mild hypertension did not differ as regards ET concentrations (13.8 +/- 2.4 fmol/ml from controls. A significant increase of PRA was recorded in severe EH (3.4 +/- 1.2 ng/ml/hour) and in CHRS with hypertension (5.2 +/- 1.3 ng/ml/hour) as well as without hypertension (5.6 +/- 1.5 ng/ml/hour)., Conclusions: The author's findings of elevated ET1,2 concentrations in subjects with a family disposition to hypertension, in advanced EH in renal hypertension and in CHRS support the assumption that ET can participate in the initial stages in the development and later in the progression of arterial hypertension either directly or by potentiating other pressor agents, e.g. higher activities of the renin-angiotensin system.

Arterial hypertension is nowadays no longer considered an isolated disorder of blood pressure regulation but a multifactorial disease with metabolic and cellular deviations. From the therapeutic aspect of thus conceived hypertension today inhibitors of the angiotensin converting enzyme seem most promising. With regard to their assumed comprehensive effect, the authors investigated simultaneously selected pressor and depressor humoral indicators and other indicators in 21 hypertensive patients with stage I and II of essential hypertension before and after three-month treatment with an angiotensin converting enzyme inhibitor lisinopril (Prinivil, Merck, Sharp and Dohme) and compared them with findings in 21 normotensive healthy subjects. Hypertensive subjects before treatment had, as compared with normotensives, significantly lower urinary kallikrein (7.8 +/- 1.2 < 18.0 +/- 4.2 EU/24hr, a significantly higher basal plasma adrenalin (1.27 +/- 0.20 > 0.54 +/- 0.20 pmol/ml) and adrenalin after a glucose load (1.26 +/- 0.22 > 0.51 +/- 0.12) and a higher relative plasma viscosity (1.74 +/- 0.02 > 1.67 +/- 0.01). The two groups did not differ significantly as to the plasma renin activity, plasma aldosterone and fibrinogen concentration and the level of urinary prostaglandins per 24 hr: 6-keto-prostaglandin F1a, thromboxane B2 and prostaglandins E and F2a. The 75 g glucose load produced an increased plasma renin, aldosterone and noradrenaline activity in normotensives as well as hypertensives before and after lisinopril treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Some metabolic and humoral deviations found in normotensive offspring from hypertensive families can be modified in the course of years either as a result of ageing or of the clinical manifestation of essential hypertension (EH). The authors compared therefore some metabolic indicators (blood sugar level, IRI, C-peptide and plasma lipids) and humoral factors (plasma catecholamines, renin activity, atrial natriuretic factor and endothelin) in four groups of subjects: 27 young normotensive sons from normotensive families (SNF) and 30 from hypertensive families (SHF) with the findings of normotonics (NT) (n = 21) and patients with EH (n = 21) by 15 years older. Despite a tendency towards higher blood sugar levels in SHF and EH, the basal as well as oGTT stimulated blood sugar values were within the normal range. They were, however, associated with higher IRI and C-peptide concentrations in SHF with a further increase in NT and a much higher increase in EH. This indicates that normal blood sugar homeostasis in these groups is achieved only by an increased insulin secretion. The reduction of the blood sugar/IRI ratio in older NT accentuated in EH, suggests an increasing insulin resistance. In the lipid spectrum the authors found an increase of total cholesterol with advancing age, this being most marked in EH where also a decline of HDL cholesterol was recorded. As to humoral factors, higher catecholamine concentrations were found in SHF. Their increase with advancing age was more marked in EH. The plasma renin activity declined with age in NT as well as in EH.(ABSTRACT TRUNCATED AT 250 WORDS)

Investigations in genetic forms of experimental hypertensions revealed certain haemodynamic, metabolic and humoral abnormalities in experimental animals already during the prehypertensive period. With regard to the obvious ratio of hereditary factors in the pathogenesis of human essential hypertension (EH), the objective of the present study was to test whether also in healthy normotensive subjects with a positive family history of EH some metabolic and humoral deviations can be detected, as compared with offspring from normotensive families. The authors compared therefore selected biochemical and humoral parameters in 20 sons of hypertensive parents (SH) with the findings in 20 sons from normotensive pa families (SN). SH had, as compared with SN, a significantly higher systolic BP (119 +/- 2.59 > 111.0 +/- +/- 2.04 mmHg). The trend of higher basal blood sugar levels 5.03 +/- 0.15 > 4.70 +/- 0.41 mmol/l) and the higher concentration of immunoreactive insulin (81.4 +/- 9.54 > 70.4 +/- after a glucose load +/- 7.78 microU/l) did not reach statistical significance. In SH plasma concentrations of adrenaline, noradrenaline and dopamine were significantly higher as well as the atrial natriuretic factor (11.7 +/- 0.77 > 8.4 +/- 0.40 fmol/ml) and of endothelin (18.2 +/- 1.70 > 12.7 +/- 0.87 fmol/ml). A load of 75 g glucose raised, as expected, the blood sugar level, IRI and C-peptide, but reduced unexpectedly the endothelin concentration in both groups. As to other biochemical parameters (fibrinogen, sodium, potassium, urea, creatinine, uric acid, cholesterol, HDL- and LDL-fractions, triacylglycerols), no significant differences were found between SH and SN. The finding of a raised mass of the left ventricle and certain differences in the diastolic and systolic left ventricular function are discussed in another paper. The results indicate that in young men with a positive family-history of EH already certain haemodynamic, metabolic and humoral deviations exist before clinical manifestation of hypertension which could contribute to later development of EH and its organ complications.

Hyperinsulinaemia and insulin resistance are associated with essential hypertension irrespective of obesity and non-insulin-dependent diabetes mellitus. One of the mechanisms whereby hyperinsulinaemia may play a role in the increase in blood pressure, is an increased activity of the sympathetic nervous system. The authors studied the incidence of hyperinsulinaemia, and the possibility of modulating it by 12-week administration of the ACE inhibitor (ACEI) lisinopril (Prinivil by MSD) at a dose of 20-40 mg/day. Compared with normotensive subjects, hypertensives showed a degree of hyperinsulinaemia and insulin resistance (higher blood glucose at higher immunoreactive insulin and C-peptide concentrations, and a higher IRI/blood glucose ratio) as well as manifestations of enhanced sympathetic activity (higher adrenaline levels). Lisinopril had a favourable effect not only on blood pressure but, also, on hyperinsulinaemia and adrenaline levels. It can be reasonably concluded that therapy with ACEI, in addition to its antihypertensive effect, may also favourably modulate some pathogenic and metabolic factors in essential hypertension.