Michael Rambausek

Vascular Effects of Parathyroid Hormone (PTH)

PTH causes dose dependent transient vasodilatation in various vascular beds, specifically renal, coeliac, coronary, but not osseous. It has an acute dose-dependent hypotensive effect in the intact animal which is not mediated by alpha- or beta-adrenergic, cholinergic or histaminergic mechanisms. Aortic medial smooth muscle cells respond to PTH with an increase of cAMP, cGMP and, presumably via protein kinase, with activation of phosphorylase B kinase. The acute vasodilatory effect of PTH is antagonised by indomethacin and diclofenac as well as by ouabain, suggesting that the membrane Na-K pump and prostaglandins are involved in PTH-induced vasodilatation. Parathyroidectomy and a high calcium diet attenuate the rise of arterial pressure in experimental hypertension, pointing to some permissive effect of PTH for development hypertension. This is most likely due to long term effects of PTH on vessel wall calcium content and exchange. This chronic effect of PTH may explain the high prevalence of hypertension in patients with primary hyperparathyroidism.

Structural causes of cardiac dysfunction in uremia

While coronary heart disease is undoubtedly a major cause of cardiac morbidity and mortality in uremia, important noncoronary problems contribute to the common presence of cardiac problems. Based on clinical and experimental studies, we could show: (i) Left ventricular hypertrophy (LVH) can be dissociated, at least in part, from elevation of blood pressure. (ii) In uremia, PTH-dependent intermyocardiocytic fibrosis occurs; it may account, at least in part, for disturbed LV compliance and contribute to the arrhythmogenic potential. (iii) Blood pressure-independent abnormalities of intracardiac arterioles and reduced myocardial capillary supply are observed.

Regulation of myocardial isomyosin V1 in uraemic rats

Abstract. Cardiac hypertrophy of various aetiologies is consistently associated with increased expression of V3 isomyosin. Uraemia is associated with cardiac hypertrophy. In the present study, we examined regulation of isomyosin in uraemic rats, using gel electrophoresis. Cardiac hypertrophy in uraemic animals was associated with a relative increase in VI isomyosin. An increased proportion of VI isomyosin was demonstrable 3 days after subtotal nephrectomy (NX 63.0 ± 8.8%; control 43.6 ± 7.2%; P < 0.01) and persisted during uraemia of 80 days duration. Elevation of VI isomyosin, relative to pair‐fed controls, was observed in uraemic animals of various age. The proportion of VI isomyosin changed in the same direction as controls when several manouevers were used which changed the isomyosin pattern, but the difference between uraemic animals and controls persisted. We studied the effect of carbohydrate loading or deprivation, starvation or administration of energetically inadequate diets, castration or administration of androgens and sodium depletion. With each of the above interventions, a difference between subtotally nephrectomized animals and sham‐operated pair‐fed control animals was statistically significant (P < 0.05). Elevation of VI isomyosin persisted during combined alpha and beta blockade and was still found when blood pressure was normalized by ACE inhibition using Ramipril. It is concluded that cardiac hypertrophy of uraemia differs from all other forms of cardiac hypertrophy by the occurrence of increased proportion of VI isomyosin. The proportion of VI isomyosin responds adequately to regulatory signals but is set at an abnormally high level.

Parathormone and blood pressure in the spontaneously hypertensive rat.

In the present communication we report on the influence of parathormone deficiency on blood pressure development in genetic, spontaneously (SH) hypertensive rats. In our study, a group of SH rats were parathyroidectomized and fed a diet with high calcium content in order to assure normal serum calcium levels.

Myopathy of Uremia

Myopathy of uremia has to some extent been a Cinderella of clinical nephrology. It is widely overlooked because signs and symptoms are usually discrete: easy fatiguability and asthenia, difficulty in performing acts involving tonic contractions of shoulder or pelvic girdles, e.g. climbing or descending stairs, arising from a squatting or kneeling position etc. On physical examination, the patients exhibit muscle weakness, particularly of the proximal muscles of the lower extremities and muscles appear flaccid on palpation.

Stimulation of Cardiac Contractility by Catecholamines is Diminished in Experimental Uremia

Cardiovascular complications are common among uremic patients. Various factors such as hypertension, anemia, acidosis, overhydration and hyperkalemia may interfere with cardiac function and explain the high cardiovascular mortality of uremic patients. Therefore, much controversy exists as to whether these factors explain the cardiac dysfunction or whether some specific “uremic cardiomyopathy” exists (1, 2). To further clarify this issue, a model of acute uremia, in which all the above factors were absent, was chosen to study myocardial performance in uremia.