The measurement of amidolytic activity in kidney homogenates for the estimation of renal kallikrein

Renewed interest in the kallikrein-kinin system was awakened in the early seventies by the suggestion that it might be involved in the regulation of sodium excretion [1, 2] or in the development of hypertension [3, 4]. However, due to complexities inherent in the measurement of the enzyme in the kidneys, only a few reports on the activity of the renal kallikrein have been published to date [5–8]

Filtration pressure response to infusion of atrial natriuretic peptides

The present experiments were undertaken to assess the effect of an atrial extract (ANF) and of the synthetic atriopeptin II (APII) on filtration pressure of rat kidneys. Continuous recordings of stop flow pressure (SFP) were made to obtain an index of the change of glomerular capillary pressure produced by atrial peptides and its time course. Short-term infusion of ANF or APII increased SFP from 40.6±0.99 to 50.7±1.42 mm Hg (p<0.001) and from 44.0±1.28 to 52.7±1.75 mm Hg (p<0.001) respectively. The maximum response was achieved promptly. Return of SFP to control was slow: 20 minutes after termination of the infusion SFP was still elevated by 4.9±1.27 mm Hg (p<0.01). Tubule and stellate vessel pressures increased less than 2mm Hg, changes that were not significant. Arterial pressure fell 6 mm Hg (p<0.05). When arterial pressure was reduced by an aortic clamp to 85–90 mmHg prior to administration of APII the response of SFP was markedly blunted (from a mean increase of 9.0±1.07 mm Hg to 4.5±0.53 mm Hg). The increase of SFP probably reflects an increase of glomerular capillary pressure. The finding suggests that atrial peptides increase glomerular filtration rate at least in part by increasing filtration pressure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47453/1/424_2004_Article_BF00586690.pd

Lithium treatment reduces the renal kallikrein excretion rate

Lithium treatment reduces the renal kallikrein excretion rate. Lithium salts are widely used agents for the prophylactic treatment of affective disorders. Lithium salts may be associated with distal nephron dysfunction. Kallikrein is a protease which is generated by the distal nephron. We used an amidolytic assay of chromatographically purified enzyme to determine the urinary excretion rate of active kallikrein in relation to lithium treatment. All plasma lithium concentrations were within the therapeutic range (0.4 to 0.9 mmol/liter). In 15 patients the urinary excretion rate of active kallikrein was 267.4 65.6 mU/24 hrs before lithium treatment, and fell to 117.8 39.6 mU/24 hrs (P < 0.05) on day 14 of lithium treatment. This reduction was associated with a decrease of immunoreactive kallikrein in the same urines by 66%. In another 15 patients who had undergone lithium therapy for an average period of 5.6 years, the urinary excretion rate of active kallikrein was 86.1 14.5 mU/24 hrs, while 21 age-matched healthy controls had an excretion rate of 364.1 58.4 mU/24 hrs (P < 0.05). Measurements of immunoreactive kallikrein in the same urine samples demonstrated a reduction of kallikrein after long-term lithium treatment by 78%. These observations could not be attributed to changes in creatinine clearance, renal sodium or potassium excretion rates or plasma concentrations of aldosterone and vasopressin. Addition of lithium to the urine in vitro had no demonstrable effect on kallikrein measurement by amidolytic assay. We conclude that lithium in therapeutic plasma concentrations may directly suppress the secretion of kallikrein by renal connecting tubule cells

A METHOD FOR INDUCTION OF CHRONIC RENAL FAILURE IN RATS

Chronic Renal Disease (CRD) is a major health burden, which has recieved increased attention in recent times and has thus become one major focus of intensive research. All is agreed that the complex interplay of major pathophysiological factors that are characteristic of CRD and end stage renal failure (ESRF) is of multifactorial aetiology. However, commonly used animal models for CRD are bedeviled by methodologically induced complexities, which make the procedures not only laborious but also make interpretation of results less explicit. More often than not, some of these procedures present in addition, pathological parameters that may not universally reflect the settings of clinical forms of CRD. We have therefore characterized a simple and reproducible method for inducing chronic renal failure (CRF) in rats; in which the pathological parameters better reflect the usual findings in clinical situations. This approach has methodological and experimental advantages with respect to commonly used procedures for inducing CRF in rats, which may involve extensive renal surgery in which the renin-angiotensin system is often markedly stimulated. This later complication is at variance with clinical CRD in which low to normal renin activity is more often the rule rather than the exception. The simplicity and reproducibility of this model, coupled with a better correlation with the known features of CRF makes it a useful rat model not only for research purposes but also for testing of therapeutic maneuvers commonly used in the clinical setting

Hormonal derangement and abnormal renal haemodynamics in the acute phase of severe burns in rats

A severe burn is characterized by the development of hyperenzymatic levels in plasma and biochemical changes in the blood as well as generalized hormonal dysregulation. This hypercatabolic state reflects the generalized enhanced proteolytic enzyme systems following severe burns. Since anuria often develops in the first hour following severe burns, we investigated the role of renal vasoactive peptides in the early events following severe scalding in order to know the extent of their involvement in the pathogenesis of deranged renal function. Male Wistar rats weighing 200 to 300 g were subjected to a 25% surface area burn by immersing their shaved dorsal surface in water at 70°C for 60 seconds under pentobarbital anaesthesia. A reduction in urinary kallikrein excretion was found (P<0.05) while the renal cortex kallikrein activity remained normal one hour after scalding. An increase in plasma renin activity (P<0.05) and a marked increase in plasma beta-endorphin concentration (P<0.005) was observed. Blood pressure was reduced in the experimental group (P<0.05). Hematocrit levels were elevated (P<0.001) and haemoglobinuria was evident in the first one hour. Plasma proteins remained unchanged. A significant reduction of urine volume was observed in the first hour (P<0.01). Plasma potassium was elevated (P<0.001) and its urinary excretion was reduced (P<0.01). The high plasma renin activity and the enhanced plasma concentration of beta-endorphin suggest that in the first hour following severe burns, hormonal derangements are mainly responsible for abnormal renal hemodynamics

Vasoactive peptides in cardiovascular (patho)physiology

Numerous vasoactive agents play an important physiological role in regulating vascular tone, reactivity and structure. In pathological conditions, alterations in the regulation of vasoactive peptides result in endothelial dysfunction, vascular remodeling and vascular inflammation, which are important processes underlying vascular damage in cardiovascular disease. Among the many vasoactive agents implicated in vascular (patho)biology, angiotensin II (Ang II), endothelin (ET), serotonin and natriuretic peptides appear to be particularly important because of their many pleiotropic actions and because they have been identified as potential therapeutic targets in cardiovascular disease. Ang II, ET-1, serotonin and natriuretic peptides mediate effects via specific receptors, which belong to the group of G-protein-coupled receptors. ET, serotonin and Ang II are primarily vasoconstrictors with growth-promoting actions, whereas natriuretic peptides, specifically atrial, brain and C-type natriuretic peptides, are vasodilators with natriuretic effects. Inhibition of vasoconstrictor actions with drugs that block peptide receptors, compounds that inhibit enzymes that generate vasoactive peptides or agents that increase levels of natriuretic peptides are potentially valuable therapeutic tools in the management of cardiovascular diseases. This review focuses on ET, natriuretic peptides and serotonin. The properties and distribution of these vasoactive agents and their receptors, mechanisms of action and implications in cardiovascular (patho)physiology will be discussed