Urinary excretion of activatable kallikrein in one-kidney pole-ligated hypertensive rats

Kallikrein activatable by trypsin was found in the urine of normal rats, corresponding to about 33% of the total kallikrein excretion. This fraction was inhibited by aprotinin and kallikrein antiserum. There was no spontaneous activation at 20 degrees C for 24 h or at 37 degrees C for 15 h which indicates that the amount detectable in the urine may represent the levels of activatable kallikrein in the renal tubule. Sephacryl S-200 chromatography of the urine disclosed the presence of two forms of kallikrein, active and activatable, with apparent molecular weights of 30 000 and 34 500 respectively. These findings allow us to assume that the activatable fraction would correspond to prokallikrein, as described by others. In hypertensive one-kidney pole-ligated rats, the total urinary kallikrein did not differ from that excreted by solely uninephrectomized rats, though the active kallikrein showed a significant drop (P less than 0.001). These results suggest that in hypertensive rats there is an alteration in the activation mechanisms of kallikrein.     

Renal kallikrein activity in spontaneously hypertensive rats

To assess possible roles of the renal kallikrein-kinin system in the development of spontaneous hypertension, we determined daily excretion of urinary total and active kallikrein in 6-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats for up to 2 weeks. We also evaluated the effect of aprotinin, a reversible inhibitor of kallikrein and other serine proteases, on the development of hypertension in the 6-week-old SHR on ordinary intakes of sodium or on sodium loading with 1% NaCl for up to 2 weeks. Active kallikrein was determined by its kininogenase activity, and the generated kinins were radio-immunologically measured. Total kallikrein was also determined by measuring kininogenase activity after inactive kallikrein had been activated with trypsin (200 micrograms/ml). Urinary active kallikrein excretion was significantly reduced in 7-week-old SHR (1.5 +/- 0.2 microgram/day compared to 2.8 +/- 0.3 micrograms/day in WKY, P less than 0.05) and in 8-week-old SHR (1.6 +/- 0.2 microgram/day compared to 3.2 +/- 0.4 micrograms/day in WKY, P less than 0.01). Urinary total kallikrein excretion was also reduced in the 7- and 8-week-old SHR whereas the ratio of active to total kallikrein did not change. In addition, renal contents of total and active kallikrein were significantly lower in the 8-week-old SHR than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Conditioned taste aversion as a function of age in mature male rats

Experimental groups of young mature (90–120 days), mature (365–395 days), and aged (730–760 days) Fischer-344 rats were allowed to drink a saccharin solution followed by lithium chloride toxicosis initiated at one of three intervals, either 15, 60, or 240 minutes. Control groups were given saline placebos according to the same schedule. In a preference test conducted 48 hours after conditioning, there was little evidence of age differences in the acquisition of a saccharin aversion. Age differences were noted in the extinction of the aversion which was tested by monitoring preference over a period of 32 days of continuous access to saccharin and water. Older animals tended to show greater resistance to extinction.     

Erythroid colony development as a function of age: the role of marrow cellular heme

The activities of the heme biosynthetic enzymes ALA synthase (ALAS) and ALA dehydrase (ALAD) and the heme degradative enzyme heme oxygenase were analyzed from bone marrow cells obtained from young, middle-aged, and senescent rats. There was age-related reduced activity of bone marrow ALAS but no age-related difference in the activity of ALAD. In contrast, heme oxygenase activity was 50% greater in the senescent marrow cells. Incorporation of 14C-glycine into heme was 45% less in senescent rat marrow cells, whereas incorporation of 14C-delta-aminolevulinic acid was not related to age. Senescent bone marrow cells demonstrated a marked reduction in 14C-leucine and 3H-uridine incorporated into protein and nucleic acid synthesis, respectively. In vitro erythroid colony (CFUE) growth by senescent bone marrow cells was as much as 40% less compared with young bone marrow cells. The decreased ability to form CFUE by the senescent bone marrow cells may be related to reduced ALAS activity and increased heme oxygenase activity. Thus, part of the aging process appears to involve fluctuations in the enzyme activities and protein synthesis involved with metabolism of heme.     

Alterations in carbonic anhydrase of the brain of rats as a function of age

Carbonic anhydrase is predominantly present in glial cells and hence has been used as a marker enzyme for the study of the changes in the brain during aging of the rat. The level of the enzyme increases till adulthood and then slightly decreases when expressed as units/g wet wt, units/mg protein and units/mg DNA. There is apparently no difference in the molecular structure of the enzyme of various ages. This indicates that the changes in its level observed during the life span may be due to regulatory changes occuring in the genome.     

Renal function of conscious spontaneously hypertensive rats

Renal clearance studies were performed in conscious 13-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) before and during volume expansion by intravenous infusion of isotonic saline. Mean arterial pressure and filtration fraction were greater in SHR, whereas fractional and absolute excretion of sodium and water, glomerular filtration rate, and renal plasma flow in SHR and WKY were not statistically different. This was the case during hydropenia and volume expansion. We did not observe as exaggerated natriuresis after intravenous loading when unanesthetized SHR were compared with the response of WKY. These observations suggest that the kidneys of genetically hypertensive rats of the Okamoto-Aoki strain have adapted to an elevated renal perfusion pressure or that hypertension is required to normalize renal function so that excretion is appropriately matched with intake.     

Aging and pancreatic exocrine function: studies in conscious male rats

Changes in pancreatic exocrine function in young (6- and 12-month-old) and old (24- to 27-month-old) male Fischer (F-344) rats were examined. Rats were prepared with cannulae draining bile and pancreatic juice separately and with duodenal and right jugular vein cannulae. Experiments were conducted between the third and the seventh postoperative day in conscious rats. Bile and pancreatic juice were returned to the intestine during both the recovery period and between experiments. Pancreatic responses to endogenous [bile-pancreatic juice (BPJ) diversion from the intestine] and exogenous stimulation [0.086, 0.432, and 1.728 nmol/kg secretin and 0.033, 0.167, and 0.667 nmol/kg cholecystokinin-octapeptide (CCK-8)] were determined. Basal secretions of fluid, bicarbonate, and protein were not affected by aging. The pancreatic responses of fluid and bicarbonate secretion to BPJ diversion or secretin were unaffected by aging. However, the increment of protein secretion in response to BPJ diversion and the largest dose of CCK-8 was attenuated in old rats. It appears the duct cell function is hardly affected by aging, but that the reserve capacity for protein secretion in response to stimulation may decrease in old rats.     

Urinary kallikrein: a physiological regulator of epithelial Na+ absorption.

The apical membrane of the mammalian urinary bladder contains two populations of ionic conductances--one Na+ selective and amiloride blockable, the other cation selective and amiloride insensitive (a leak channel). Addition of kallikrein (an enzyme of unknown function normally found in urine) to the mucosal solution of the mammalian urinary bladder epithelium resulted in the loss (over a 2-hr period) of amiloride-sensitive Na+ current and an increase in the leak current that is amiloride insensitive. The rate of hydrolysis of Na+ channels is a first-order process that is concentration (activity) dependent and described by simple Michaelis-Menten kinetics with a maximum rate of 9.5 X 10(-3) min-1. At the activities measured in human urine, the corresponding rate constant will decrease Na+ channel density by 99.5% in 24 hr. Amiloride protects the amiloride-sensitive Na+ channels from degradation but not the leak pathway. The rate of hydrolysis of the leak pathway as well as the kinetics of hydrolysis are the same as that described for the Na+ channel. Of interest is that the leak pathway is hydrolyzed into a form that seems to partition between the apical membrane and mucosal solution (an unstable leak pathway). These results and previous findings suggest a regulatory role for kallikrein in salt and water homeostasis.     

Motor performance of women as a function of age and physical activity level

In Study 1, simple and choice reaction time, balance, sit and reach flexibility, shoulder flexibility, and grip strength of older active women were compared with older inactive women, and active and inactive younger women. Except for grip strength, scores of older active women on all measures were significantly better than for older inactive women, and much more like those of the younger women. In Study 2, scores of avid women golfers were compared with the older active and inactive women from Study 1. On all variables, the scores of golfers were significantly better than those of the older inactive women, but not significantly different from the older active women. Findings were consistent with previous research on men, indicating that motor performance tends to be more highly related to lifelong physical activity level than to age.     

Changes in hemodynamics with advancing age in conscious spontaneously hypertensive rats

The changes of hemodynamics were measured in spontaneously hypertensive rats (SHR) of increasing ages. Male SHR and Wistar rats of the Kyoto strain (WKY) at 4, 12, 24 and 48 weeks of age were used. The right jugular vein and the left femoral artery were cannulated and a thermistor was placed in the ascending aorta. After 24-hour rest, heart rate (HR), mean arterial pressure (MAP) and cardiac output (CO) were measured. The ratio of left ventricular weight (LVMI) of 4 week-old SHR had already increased significantly when compared to WKY. The HR in 4-week-old SHR was significantly higher than WKY. The increased HR in young SHR indicates the hypersensitivity of the sympathetic nervous system. Increased CO in 4 week-old SHR was due to high HR. The ratio of heart work to left ventricular mass (HW/LVM) of SHR at all age groups was not different from that of WKY, although the ratio of heart work to body weight (HWI) had a tendency to rise in SHR as compared to that in WKY. Our conclusion is that the development of LVM adapts to HW.     

Reaction and movement time as a function of age and physical activity level.

The SRT, DRT, and MT of older men (OA) who have experienced a life style of chronic physical activity were compared to those of nonactive men of similar age (ONA), and also to active (YA) and nonactive young men (YNA). Although activity level and age were significant factors, most of the activity level-by-age interaction in all but DRT was attributed to the slower performance of the ONAs. At least in this study, a life style of physical activity appeared to play a more dominant role in determining SRT, DRT, and MT than age. The hypothesis that most of the slowing of responses in the aged is attributable to CNS processing rather than MT decrements is repudiated, since MT results paralleled those of SRT and DRT.     

Urinary neopterin index as a measure of rheumatoid activity

The urinary neopterin index (U-NEOPT-I), expressed as micro-moles of neopterin/moles of creatinine) of 67 patients with definite or classical rheumatoid arthritis was significantly higher than that of sex- and age-matched persons or of 24 non-matched patients suffering from osteoarthrosis or arthralgia (2p less than 0.001). Furthermore, the patients with active disease had statistically significantly increased U-NEOPT-I when compared with patients with a clinically less active disease. In this study, the U-NEOPT-I value was the equal of CRP as a measure of rheumatoid activity. We suggest that neopterin might be involved in the pathogenesis of rheumatoid arthritis.