The renin-angiotensin-aldosterone system, antidiuretic hormone levels and water balance under tocolytic therapy with Fenoterol and Verapamil.

The effects of long-term infusion of fenoterol (a beta 2-sympathomimetic drug) in combination with the calcium antagonist verapamil on water balance, the renin-angiotensin-aldosterone system and antidiuretic hormone during pregnancy were studied. Within two hours of the start of infusion, plasma renin and antidiuretic hormone levels were significantly increased, but plasma aldosterone was strongly decreased. There was a concomitant marked reduction of urinary, sodium, and potassium excretion and a decreased creatinine clearance. The long-lasting reduction of urinary excretion which resulted in an elevated water retention is apparently due to other unknown factors. Results are discussed with special regard to the relationship between water balance disturbances and pulmonary edema.

[High dose betablocker treatment in experimental renal hypertension (author's transl)]. / Hochdosierte Anwendung von beta-Rezeptorenblockern bei experimenteller renaler Hypertonie.

Rats with experimental renovascular hypertension were treated with high doses of beta-blocking agents. Pindolol 10 mg/kg per day increased Goldblatt-type hypertension, whereas Propranolol 100 mg/kg per day showed an antihypertensive effect. A linear correlation between the weight of the left-heart ventricle and the systolic blood pressure was found in animals treated with Pindolol as well as in untreated Goldblatt rats. On the contrary, the weights of the left-heart ventricle were significantly higher in those animals treated with Propranolol than in the other groups. The results show that Pindolol in high doses, possibly on account of its sympathomimetic activity, leads to an increase in Goldblatt hypertension, but does not influence the pressure-dependent progression of left-heart hypertrophy. On the other hand, Propranolol, possibly on account of a cardiodepressory effect, leads to a decrease in blood pressure.

[Oral contraceptives, hypertension and nephrosclerosis]. / Ovulationshemmer, Hypertonie und Nephrosklerose.

Oral contraceptives are of pathogenetic importance in hypertension of women aged 26 to 35 years. The hypertensive reaction occurs predominantly in those women who have hereditary predisposition to hypertension or diabetes mellitus, who suffer themselves from diabetes or who showed toxemia in previous pregnancies. Our findings are not in agreement with the suggestion that oral contraceptive hypertension in women is always reversible. Simultaneous administration of estrogen and progestogen accelerates Goldblatt-type hypertension in rats. Neither estrogen nor progestogen alone alters arterial blood pressure. In the hormonal combination the hypertensive effect of estrogen can be replaced by epsilon-aminocapronic acid. Estrogen is the only substance increasing plasma renin activity. There is no correlation between the increase of blood pressure and the plasma renin activity in the various groups of experimental animals receiving the different pharmacological substances. Estrogen and the synthetic progestogen cause sodium retention. Because of this, oral contraceptive hypertension may be supposed not to result from a stimulation of the renin-angiotensin-system. Oral contraceptive hypertension may result from a combination of endothelial lesions due to the estrogen's effect on blood coagulation leading to nephrosclerosis, and sodium retention produced predominantly by the synthetic progestogen.

PIP: The results of 2 studies to determine the relationship between hormonal contraceptive (h.c.) use, hypertension, and nephritis are reported. 828 women, 16-50 years of age, were divided into 3 groups. 1 group had never used h.c.s., 1 group was presently using h.c.s., and 1 group had used h.c.s. for the last time more than a year prior to the study. Women 26-35 years of age who were using h.c.s. at the time of the study more often developed hypertension than other groups. The h.c. users who developed hypertension more often had a family history of hypertension or diabetes mellitus, more often had diabetes themselves, and more often suffered from preeclampsia or eclampsia during pregnancy. In a second study, ethinyl estradiol, norethisterone acetate, epsilon aminocapronic acid, desoxycorticosterone acetate, and table salt were administered singly or in combinations to 2 groups of rats. In one group, a Goldblatt-type hypertension was induced with a clamp on the nephric artery. No increase in blood pressure was observed in animals which received only an estrogenic or progestagenic agent. Significant increases in blood pressure were observed in animals that were given combinations of estrogenic and progestagenic agents, however. Significantly increased plasma-resin activity was observed in all animals which were given estrogen, while animals receiving desoxycorticosterone acetate showed a highly significant decrease in plasma-renin activity.

[Hypertension therapy during pregnancy and lactation (author's transl)]. / Hochdrucktherapie während Schwangerschaft und Stillperiode.

Hypertension in pregnancy is not only of importance to the mother, for whom there is an increased risk of cardiovascular damage, but also for the unborn child because it leads to a reduction of blood flow in the uteroplacental unit and consequently to a disturbance of growth and maturation. Reduction of blood pressure by drugs lowers the incidence of cardiovascular diseases in the mother in the same way as outside pregnancy. There is, however, a well-founded suspicion that the blood flow in the uteroplacental unit may be still further reduced by some antihypertensives, at least in certain situations. Therefore careful consideration must be given to which antihypertensives can be used during pregnancy and which cannot.

[Drug therapy of the kidney patient]. / Die medikamentöse Therapie des Nierenpatienten.

In patients suffering from renal failure pharmacological therapy is performed to influence the causal disease, to mitigate symptoms of the uremic syndrome, or to treat additional illness. Immunosuppressive therapy may be initiated in patients with rapidly progressive glomerulonephritis. Anemia and osteopathia have to be treated in most patients with renal insufficiency. Medication with antibiotics and digitalization shows special aspects in patients with impaired renal function.

[Kidney damage caused by drugs]. / Nierenschäden durch Arzneimittel.

Drugs may induce functional or organic lesions of the kidneys. Organic lesions may consist of glomerulonephritis, interstitial nephritis, and/or toxic tubular necrosis. Clinical symptoms may include temporary deterioration of the renal function, acute but reversible renal failure, or chronic progressive uremia calling for dialysis treatment.

[Pregnancy in women with diabetic nephropathy--a clear indication for antihypertensive treatment]. / Schwangerschaft bei Frauen mit diabetischer Nephropathie--eine klare Indikation zu einer antihypertensiven Behandlung.

Manifestation and progression of diabetic nephropathy is very much influenced by the high of blood pressure values. There is evidence that not pregnancy per se aggravates the disease but only deterioration of blood pressure control.

[Treatment with anticoagulants in glomerulonephritis (author's transl)]. / Antikoagulantienbehandlung bei Glomerulonephritis.

Four patients with different forms of glomerulonephritis were treated with the anticoagulant heparin (Liquemin) or phenprocoumon (Marcumar). Following the results in these cases and the experiences of other research groups, which have been published in the last few years, we have tried to lay down a scheme for treatment with anticoagulants in glomerulonephritis. Such a treatment is recommended in peracute or rapid progressing glomerulonephritis, in forms of the disease of which is known that they have a poor prognosis, and in situations in which the risk of simultaneous thromboembolic complications as a result of a nephrotic syndrome represents a further argument for the use of anticoagulants.

[The pathogenesis of oral contraceptive hypertension (author's transl)]. / Untersuchugen zur Pathogenese der Ovulationshemmer-Hypertonie

Simultaneous administration of estrogen and progestogen accelerates Goldblatt-type hypertension in rats. Neither estrogen nor progestogen alone alters arterial blood pressure. In the hormonal combination the hypertensive effect of estrogen can be replaced by epsilon-amino-capronic acid and the hypertensive effect of progestogen by desoxycorticosterone acetate. Estrogen is the only substance increasing plasma renin activity. There exists no correlation between the increase of the blood pressure and the plasma renin activity in the various groups of experimental animals receiving the different hypertensive preparations. Because of this, oral contraceptive hypertension may be supposed not to result from a stimulation of the renin-angiotensin system but may easily be seen in a combination of endothelial lesions and sodium retention, the former being caused by the estrogen's effect on blood coagulation, the latter produced by the synthetic progestogen.

PIP: An animal study to determine the effect of oral contraceptives on blood pressure is reported. A clamp was placed on the renal artery of a group of 18 Wistar rats to induce Goldblatt hypertension. This group and another group of 18 rats were given various dosages of ethinyl estradiol, norethisterone acetate, epslon-amino-capronic acid (as a substitute for inducing an estrogenic hypertensive effect), and/or deoxycorticosterone acetate or salt (as a substitute for induction of a gestagenic hypertensive effect). A significant increase in blood pressure was recorded only among the rats with induced Goldblatt hypertension which were administered both an estrogenic and gestagenic agent. All animals that were administered estrogen showed a significant increase in the plasma-renin activity (PRA). Animals that were administered deoxycorticosterone acetate showed a highly significant decrease in PRA.

[Clinical course and pathogenesis of oral contraceptive hypertension (author's transl)]. / Klinik und Pathogenese der Ovulationshemmer-Hypertonie.

Oral contraceptives are of pathogenetic importance in hypertension of women aged 26 to 35 years. The hypertensive reaction occurs predominantly in those women who have hereditary predisposition in hypertension or diabetes mellitus, who suffer themselves from diabetes mellitus or who showed toxemia in preceding pregnancies. Experimental studies in rats indicated that oral contraceptive hypertension could be due to vascular lesions, produced by estrogen, and sodium retention, caused by progestogen. Our findings are not in agreement with the proposal that the hypertensive reaction in women is always reversible. It would be of advantage if oral contraceptives could be used, which contain no estrogen or at least estrogen in the lowest possible dose and which comprise progestogens without sodium-retaining effect.

PIP: Ovulation inhibiting oral contraceptives have an important pathological significance for the development of hypertension in women between the ages of 26-35. A hypertension reaction to oral contraceptives occurs predominantly in women who have a hereditary predisposition to hypertension or diabetes mellitus, who suffer themselves from diabetes mellitus, or who have shown toxemia in a previous pregnancy. Studies with rats show that hypertension could be due to vascular lesions, produced by estrogens, and by sodium retention, caused by progestagen. The reversibility of oral contraceptive hypertension is considered doubtful, contrary to other studies. The optimum oral contraceptive would be 1 that could eliminate the estrogen component, or at least minimize it, and which would be comprised of progestagens which would not cause sodium retention.

[Are clotting disorders a pathogenetic factor in nephrosclerosis and hypertension? (author's transl)]. / Blutgerinnungsstörungen, ein pathogenetischer Faktor für Nephrosklerose und Hochdruck?

The clinical course of the haemolytic-uraemic syndrome in four patients suggests that hypertension may result from it. The morphological changes in the kidney are those of primary malignant nephrosclerosis. Hypercoagulability is thought to be an important pathogenetic factor in the development of the disease. But irreversible renal failure is not, contrary to typical primary malignant nephrosclerosis, an inevitable sequel. Abortive forms with predominant involvement of glomerular vessels have a more favourable prognosis than those forms with additional preglomerular vascular changes, in which a more or less marked impairment of renal function and hypertension persists. These forms are of particular interest because they indicate a renal pathogenetic mechanism of chronic hypertension. The described observations--taken together with those on the pathogenesis of hypertension caused by oral contraceptives--provide a pointer to the importance of clotting disorders in the initiation and development of some forms of hypertension.

[The influence of the beta-blocking agent pindolol on blood pressure and heart weight of rats with Goldblatt-type hypertension (author's transl)]. / Der Einfluss des beta-Receptoren-Blockers Pindolol auf Blutdruck und Herzgewicht bei Ratten mit Goldblatt-Hypertonie

Preexisting increase of plasma renin activity in hypertension seems to indicate an effective hypotensive action of adrenergic beta-receptor antagonists. In spite of marked elevation of plasma renin activity in Goldblatt-rats, the beta-blocker Pindolol failed to lower the blood pressure. On the contrary, high doses of this substance led to an acceleration of the Goldblatt-type hypertension, perhaps because of the intrinsic sympathomimetic activity of Pindolol. These findings support the conception that beta-blockers are effective in lowering the blood pressure only in hypertension with stimulated renin secretion, which is caused by an increased activity of the sympathetic nervous system. Plasma renin activity was not altered by Pindolol. There existed a linear relationship between blood pressure and left-ventricular weight in all groups of rats, which was not impaired by Pindolol in all used doses.

[Pulmonary edema during tocolytic treatment (author's transl)]. / Zur Frage des Lungenödems bei der tokolytischen Therapie.

During tocolytic treatment with Beta 2-Sympathomimetic drugs pulmonary edema is occasionally observed. The cause remains uncertain. Within 48 hours after the onset of treatment marked water retention is observed. The weight increases, the hemoglobin decreases the hematocrit decreases, the albumin concentration decreases, the water and sodium excretion decreases. The pathogenesis is discussed and recommendations for the management are proposed. Water retention due to tocolytic treatment in addition to the physiologic water retention of pregnancy or in addition to pre-eclampsia cortisone treatment, renal insufficiency, or treatment with intravenous infusions may lead to a hypervolemia which can no longer be compensated by diuresis and therefore can lead to pulmonary edema. A list of 10 groups of patient with a high risk is described. These require thorough observation following tocolytic treatment.

[Hyperparathyroidism and metabolic acidosis (author's transl)]. / Hyperparathyreoidismus und metabolische Acidose.

Severe secondary hyperparathyroidism and marked metabolic acidosis occurred in five patients in advanced renal failure due to chronic interstitial nephritis. In all instances there was an immediate and lasting rise in plasma standard bicarbonate concentration after subtotal parathyroidectomy. These observations suggest that the metabolic acidosis in some patients with advanced renal failure is, at least in part, due to hyperparathyroidism and, therefore, responsive to its appropriate treatment.

[Oestrogen as a risk factor for the vascular system (author's transl)]. / Ostrogen als Riskikofakter für das Gefsssystem.

Plasma oestradiol and testosterone concentrations were measured in 44 men with angiographically proven coronary heart disease, 66 men without evidence of coronary heart disease serving as control. Another group consisted of 28 men with renal failure. Those with coronary heart disease had a significantly higher oestradiol concentration than the control group. This increased value also was present in patients with renal failure. There was a relationship between the level of oestradiol on one hand and glucose tolerance, ratio of beta to alpha-lipoproteins and blood pressure, on the other, in both the patients with coronary heart disease and the healthy controls. These results indicate the oestradiol may in males be an indicator of a risk constellation of vascular damage. Perhaps, it may be the cause of an abnormal carbohydrate and fat metabolism, which then leads to hypertension and degenerative vascular lesions.