W. Kreusser

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.

Effect of parathyroid hormone, calcitonin and growth hormone on cAMP content of growth cartilage in experimental uraemia

Abstract. The response of proximal tibial growth cartilage cAMP content to different hormonal stimuli, i.e. parathyroid hormone, calcitonin and somatotropic hormone was evaluated in rats with bilateral or subtotal nephrectomy. In uraemic rats, basal cAMP content of growth cartilage was unchanged. Administration of 1–34 PTH in vivo or incubation of growth cartilage with 1–34 PTH in vitro caused a significantly smaller increment of cAMP in uraemic rats (40 IU PTH in vivo: 11·4±1·01 pmol cAMP/mg protein; controls 24·0±2·55; P<0·001). This finding implies PTH resistance. Diminished cAMP response in uraemic animals was not changed by pretreatment with 1,25(OH)2D3 or parathyroidectomy. The increment of cAMP content of growth cartilage of uraemic animals was significantly (P<0·01) greater after in vivo administration of 10 IU calcitonin (46·1±4·89 pmol/mg protein; control: 29·0±3·99) or incubation of cartilage with calcitonin in vitro. This finding implies overresponsiveness to calcitonin. Neither in acute nor in chronic uraemia, STH caused a significant change of cartilage cAMP or cGMP content, but STH stimulated 3H‐thymidine incorporation into chondrocytes of rats with 5 days uraemia (solvent 2·98±0·51 times 103 cpm per cartilage; STH 5·08±0·34; P<0·05) and caused significant improvement of longitudinal growth of rats with 20 days uraemia.

Haemodynamics and myocardial metabolism of phosphorus depleted dogs: effects of catecholamines and angiotensin II

Abstract. The responses of arterial pressure and myocardial contractile force (VPM) to infusion of angiotensin II, noradrenaline and orciprenaline were examined in twelve dogs during a control phase, after 30 days of dietary phosphorus deprivation and after 21 days of phosphorus repletion. In the phosphorus depletion period, animals had low skeletal and heart muscle Pi content, low magnesium, ATP and creatine phosphate in skeletal and heart muscle with no change of ADP, AMP or energy charge. In the basal state, VPM was diminished with no change of end‐diastolic and systolic pressure. Infusion of angiotensin II caused a significantly smaller rise of arterial pressure (angiotensin II resistance), and the stimulatory effect of noradrenaline and orciprenaline on VPM was diminished (catecholamine resistance). These effects were reversible with Pi repletion.

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.

Cardiac Function and Metabolism in Phosphorous Depleted Dogs — Effects of Hormonal Stimulation

Phosphorous depletion has recently been recognized as a cause of myocardial dysfunction in humans (1) and animals (2). O’Connor et al. (1) observed low stroke volume in acutely hypophosphatemic alcoholic patients. This abnormality returned to normal upon administration of phosphorous despite no change or even reduction of preload. Furthermore, in chronically phosphorous depleted patients, Darsee and Nutter (3) described a form of hypophosphatemic cardiomyopathy reversible upon phosphorous repletion. Finally, Fuller et al. (2) could reproduce the deleterious effect of phosphorous depletion on cardiac function in dogs with selective hypophosphatemia induced by dietary phosphorous depletion. The authors found a reversible depression of myocardial performance, i.e. of stroke volume, peak blood flow velocity and acceleration. These previous investigations were restricted to basal hemodynamic conditions and no information is available on the cardiac response to catecholamines.

Circulatory Response to Pressor Agents in Phosphorous Depletion

Impaired function of myocardial muscle is a known feature of phosphorous depletion (PD) in man (1,2) and in experimental animals (3). Congestive heart failure has been described in patients, who were chronically phosphorous depleted secondary to ingestion of phosphorous binding agents (2). Furthermore, abnormalities of skeletal muscle function are common in PD (4). However, no information is available on smooth muscle function in PD. Specifically, control of blood pressure and the peripheral response to pressor agents has not been studied.

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.