Effects of adrenergic nervous system and catecholamines on systemic and renal hemodynamics, sodium and water excretion and renin secretion

The influences of the adrenergic nervous system on various organ systems in the body are protean. No attempt will be made in this review to survey these many effects; but rather the focus will be on the specific influences that adrenergic tone and catecholamines exert on systemic and renal hemodynamics, the excretion of sodium and water excretion and the secretion of renin. Where possible, emphasis will be placed on the integration of these functions into a ideologically oriented system of control of systemic hemodynamics and of body fluid volume and composition, including the implications for the pathogenesis of disease states

Cardiorenal Syndrome in Acute Heart Failure Syndromes

Impaired cardiac function leads to activation of the neurohumoral axis, sodium and water retention, congestion and ultimately impaired kidney function. This sequence of events has been termed the Cardiorenal Syndrome. This is different from the increase in cardiovascular complications which occur with primary kidney disease, that is, the so-called Renocardiac Syndrome. The present review discusses the pathogenesis of the Cardiorenal Syndrome followed by the benefits and potential deleterious effects of pharmacological agents that have been used in this setting. The agents discussed are diuretics, aquaretics, natriuretic peptides, vasodilators, inotropes and adenosine α1 receptor antagonists. The potential role of ultrafiltration is also briefly discussed

Norepinephrine-induced acute renal failure: A reversible ischemic model of acute renal failure

Several studies have shown that acute renal failure (ARF) can be produced in the dog by infusing norepinephrine (NE) into a renal artery [1, 2]. In these studies the injury appeared to be confined to the infused kidney, with no changes occurring in systemic hemodynamics or in the function of the contralateral kidney. The hemodynamic changes noted in the infused kidney were comparable to those seen in human ARF. A major criticism of these studies, however, is that the renal failure was not shown to be reversible, as it typically is in man. In the present study, we have reexamined the NE-induced model of ARF in the dog with the particular purpose of finding a set condition which would cause ARF and yet allow recovery of renal function within a period of time comparable to that usually seen in the human disease

Verapamil protects against progression of experimental chronic renal failure

Verapamil protects against progression of experimental chronic renal failure. Chronic administration of verapamil (Ver) decreases nephrocalcinosis and tubular ultrastructural abnormalities in the remnant model of chronic renal disease. In the present study, the effect of chronic Ver administration on renal function, renal histology and mortality after subtotal nephrectomy was examined. Fourteen days after staged subtotal nephrectomy rats were paired according to renal functional impairment, mean arterial pressure (MAP), and body weight. Rats were pair fed and received either Ver (0.1 µg/g sc bid, N = 10) or saline (0.1ml sc bid, N = 10) for up to 23 weeks. Both members of each pair were sacrificed shortly before the uremic death of controls. At sacrifice, rats treated with Ver had a lower serum creatinine (2.29 vs. 2.99 mg/dl, P < 0.05) and a higher creatinine clearance (318 vs. 164 µl/min, P < 0.05) than controls. In a second experiment, survival was superior in rats treated with Ver than in controls from week seven (P < 0.0025 by week 14). Serum creatinine was higher at week 10 in control rats (1.68 vs. 1.10 mg/dl, P < 0.05). MAP was no different between the two groups, irrespective of the time between Ver administration and the measurement of MAP. Histological damage and nephrocalcinosis were worse, and renal and myocardial calcium content was higher in controls. In conclusion, independent of any effect on systematic MAP, chronic administration of Ver protects against renal dysfunction, histological damage, nephrocalcinosis and myocardictl calcification, and improves survival in the remnant model of chronic renal disease

Factors determining renal response to water immersion in non-excretor cirrhotic patients

Factors determining renal response to water immersion in non-excretor cirrhotic patients. Non-excretor cirrhotic patients, defined by their inability to normally excrete a standard water load, display variable responses to head–out water immersion. The hemodynamic, hormonal, and renal functional status of fifteen such patients were analyzed relative to water excretion during head-out water immersion. Group 1 patients (N = 7) all excreted less than 40% of the water load during immersion, whereas excretion was greater than 40% in all eight patients in Group 2. Group 1 patients, when compared with Group 2, had more ascites, more diuretic resistance, lower serum sodium concentration (125 ± 2 vs. 130 ± 1 mEq/liter, P < 0.05), and more impaired baseline water excretion (12.9 ± 1.2 vs. 35.9 ± 5.9% of water load in 5 hr, P < 0.005). Systemic hemodynamic responses to water immersion were similar in both groups. Glomerular filtration rate and renal plasma flow were significantly more impaired in Group 1 patients (inulin clearance 28 ± 6 vs. 62 ± 9 ml/min/1.73m2, P < 0.05; para-aminohippurate clearance 212 ± 35 vs. 357 ± 37 ml/min, P < 0.05). Concentrations of plasma vasopressin (1.7 ± 0.5 vs. 0.8 ± 0.1 pg/ml, P < 0.05), renin (8.6 ± 1.7 vs. 3.8 ± 0.9 ng/ml/hr, P < 0.05), aldosterone (82 ± 14 vs. 39 ± 10 ng/dl, P < 0.05) and norepinephrine (1155 ± 183 vs. 603 ± 126 pg/ml, P < 0.05) were all significantly higher in Group 1 than Group 2 patients during water immersion. Thus, non-excretor cirrhotic patients are not homogenous and appear to comprise a spectrum with those patients in whom water excretion is most impaired, having tense ascites, diuretic resistance, lower serum sodium concentrations, more impaired renal function, and more marked abnormalities in the hormonal markers of decreased effective blood volume

A new method for studying human polycystic kidney disease epithelia in culture

A new method for studying human polycystic kidney disease epithelia in culture. Human polycystic kidney disease (PKD) epithelia were successfully grown in culture and expressed abnormal characteristics. Cysts lining epithelia of superficial and deep cysts were microdissected and compared to individual normal human proximal straight tubules (PST) and cortical collecting tubules (CCT) grown in defined media. PKD cyst epithelia differed from normal renal tubular epithelia in growth patterns and structural and functional properties. PKD epithelia grew more rapidly and showed cyst–like areas in otherwise confluent monolayers. Polygonal and elongate cells contained an epithelial–specific cytokeratin antigen and had polarized morphology. An extremely abnormal basement membrane morphology was seen and consisted of some banded collagen and numerous unique blebs or spheroids. These blebs were apparently extruded from intracellular vacuoles and stained with ruthenium red, suggesting a proteoglycan component. Cytochemistry of marker enzymes demonstrated the presence of NaK-ATPase and alkaline phosphatase, but a lack of γ-glutamyl transpeptidase. The response of adenylate cyclase activity to vasopressin, parathyroid hormone, and forskolin was significantly diminished in PKD cells as compared to PST and CCT. These studies suggest a defect in cell growth and basement membrane synthesis in human PKD. Cultured PKD epithelia provide a new tool for the study of the pathogenesis of this disease