Kallikrein In Rats Research Articles

Effect of norepinephrine and renal denervation on renal PGE2 and kallikrein in rats.

To investigate the influence of the sympathetic nervous system on the renal prostaglandin and kallikrein systems we studied the effects of norepinephrine (NE) infusion and renal denervation on the urinary excretion of prostaglandin E2 (PGE2) and kallikrein in unanesthetized rats. Relative to sham controls, in rats infused with NE at 15 micrograms/h i.p. for 8 days. plasma NE was increased 10-fold, systolic blood pressure by 20-34 mmHg, and urinary PGE2 excretion twofold, but urinary kallikrein excretion was not altered. Norepinephrine infusion also produced a transient natriuresis and a slight reduction in body weight gain. Relative to values in sham-operated rats, bilateral renal denervation reduced catecholamine content of the kidneys to less than 10% of control 10 and 30 days after surgery, but had no effect on urinary excretion of either PGE2 or kallikrein. It is concluded that in unanesthetized rats a) renal kallikrein is not affected by either a sustained increase in plasma norepinephrine or by chronic renal artery denervation, b) basal renal PGE2 production is not regulated by basal renal nerve activity, and c) prolonged elevation of plasma norepinephrine causes, either directly or indirectly, a sustained induction of PGE2 production by the kidney.

Effects of dexamethasone on excretion of urinary kallikrein and urinary protein in Dahl salt-sensitive and salt-resistant rats.

The effect of glucocorticoid treatment on urinary kallikrein excretion was assessed in Dahl salt-hypertension susceptible (S) and salt-hypertension resistant (R) rats. A single dose of dexamethasone (100 micrograms) caused a marked water diuresis and a slight decrease in urinary kallikrein excretion in both S and R rats. A single dose of dexamethasone also caused the S rat to excrete massive amounts of protein into the urine, almost 3-fold higher than S rats treated with oil; the effect on R rat urinary protein was similar, but less severe. Daily administration of dexamethasone (100 micrograms/day) for 7 days caused marked suppression of urinary kallikrein excretion in both S and R rats. Increased urinary protein following chronic treatment was still evident in the dexamethasone-treated S rats but not in the dexamethasone-treated R rats. Chronic glucocorticoid treatment probably inhibits urinary kallikrein activity by suppressing pituitary and adrenal function which would remove the stimulatory effect of aldosterone on urinary kallikrein excretion. There was no evidence for a stimulatory role of glucocorticoids on urinary kallikrein.

Urinary kallikrein and hypertension in cadmium-exposed rats

Chronic exposure of rats to cadmium (Cd) in drinking water induced elevated systolic and diastolic blood pressure. Heart rate, however, was lowered, suggesting that the hypertension in these rats may be due to an increase of the total peripheral resistance, possibly involving a central nervous system (CNS) component in Cd-induced hypertension. Urinary kallikrein activity was reduced in the exposed animals and may explain the previously reported antinatriuretic effect of Cd, since renal kallikrein is an enzyme responsible for the synthesis of kallidin, a potent vasodilator and natriuretic polypeptide.

Origin of Kallikrein in Rat and Human Exocrine Glands and Kidney

1. The cellular localization of kallikrein was investigated in rat and human exocrine glands and kidney by a direct immunofluorescence technique. 2. Kallikrein was found in the duct system of the rat and human major salivary glands. 3. Kallikrein was found in the distal tubular cells of the rat kidney. Attempts to localize kallikrein in the human kidney were unsuccessful. 4. In the rat and human pancreas, kallikrein was found as a pro-enzyme in the acinar cells.

Inhibition of Urinary Kallikrein Excretion by Semi-Purified Renin in the Rat

1. Rat kidney extracts obtained at successive stages of a purification procedure, which allows the separation of renin and kallikrein, were used in order to investigate their effect upon urinary excretion of kallikrein, sodium, potassium and water in hyperhydrated rats. 2. Only the purified fraction containing renin reduced kallikrein excretion. The decrease of kallikrein coincided with a considerable increase in sodium, potassium and water excretion. 3. The natriuretic effect of renin extract did not depend on the presence of kallikrein. The injection of a mixture of renin and kallikrein attenuated the effect of renin alone, indicating that both enzymes exert antagonistic actions on the excretion of electrolytes and water by the kidneys. 4. A purified fraction of kidney extract containing no kallikrein and only traces of renin activity, had a stimulatory effect on kallikrein, water and electrolyte excretion.

241 - Effects of neomycin on plasma renin activity and urinary excretion of kallikrein in rats

241 - Effects of neomycin on plasma renin activity and urinary excretion of kallikrein in rats

Application of bradykinin radioimmunoassay for the measurement of urinary kallikrein activity rats.

Bradykinin radioimmunoassay was applied for the measurement of urinary kallikrein activity in rats. Antisera against bradykinin were raised in rabbits by injecting synthetic bradykinin coupled to human serum albumin via a difluorodinitrobenzene reaction. For radioimmunoassay a high titre antibody was used at a final dilution of 1:65000 to bind approximately 8,000 cpm of [125I]-tyrosine8-bradykinin. Standard curves were plotted from synthetic bradykinin samples (1--1000 pg). Kinins were generated by incubating partially purified kininogen with rat urine in the presence of kininase inhibitors. Bradykinin antiserum showed crossreaction with kallidin, met-lys-bradykinin and dog-kininogen. To eliminate interference of the kininogen with kinin radioimmunoassay, alcohol precipitation of the substrate was performed after incubation. Concentration of urinary kallikrein in rats showed no significant difference between day and night 12-hours-colllecting period. Total kallikrein excretion at night, however, was about twofold higher, correlating to a twofold higher urine volume during the night.

Renal urinary kallikrein in normotensive and hypertensive rats during enhanced excretion of water and electrolytes.

1. Urinary kallikrein excreted by normal rats is significantly increased (P less than 0-001) 2 h after: (a) water loading, (b) water loading plus frusemide, 0-27 mmol (10 mg) per rat, (c) salt loading. In water-loaded rats, 5 i.u. of renin strikingly reduced kallikrein excretion (P less than 0-01) but considerably increased sodium excretion (P less than 0-001). 2. Renal kallikrein, measured by its kininogenase activity within 2 h of water loading, was significantly increased (P less than 0-05); after water loading and frusemide it was 40% decreased (P less than 0-001) and after salt loading it was reduced by approximately 50% (P less than 0-02). Renin did not change renal kallikrein. 3. Severely hypertensive (one-kidney) rats (blood pressure greater than 150 mmHg) showed no increase of urinary kallikrein after water loading, although there was a marked natriuresis, in moderately hypertensive rats (blood pressure less than 150 mmHg) urinary kallikrein was only one-third of that observed in control normotensive rats, after an equal degree of water loading.

Urinary kallikrein excretion in a spontaneously hypertensive strain of rats.

Concentration and 24-hr excretion of urinary kallikrein in spontaneous hypertensive Wistar strain rats of both sexes obtained by selected inbreeding (25th generation) are significantly decreased as compared with the excretion in normotensive inbred rats (24th generation) descending from common ancestors. Apparently in these hypertensive rats there is an abnormal capacity of the kidneys to produce or release kallikrein, but more studies will be necessary to correlate this findings with blood pressure increase.

Effect of furosemide upon urinary kallikrein excretion.

Having in mind the significant decrease of urinary kallikrein in rat with renal hypertension and in humans with essential hypertension, the effects of furosemide on kininogenase activity has been studied in urine of normal and hypertensive rats which received tap water or a 1% NaCl solution for drinking. Administration of 20 mg furosemide which produces maximal diuretic effect in normal rats, induced in these animals a 150–200% increase of the excretion of this enzyme after 8 hours, when compared to the activity measured before giving the drug. This increase which is observed in the normal rats drinking either water or a 1% NaCl solution shows a significant correlation with the excretion of sodium, potassium and water. In hypertensive rats, in 7 or 9 cases, an increase of kallikrein excretion (200–600%) is observed, which does not reach the levels of excretion in normal untreated rats. Furosemide did not produce increase of urinary kallikrein in hypertensive rats drinking 1% NaCl solution.

Effects of mineralocorticoids, altered sodium intake, and adrenalectomy on urinary kallikrein in rats.

The urinary excretion of kallikrein was examined in rats whose mineralocorticoid level was increased by the administration of deoxycorticosterone or a low-sodium diet and decreased by adrenalectomy. Administration of deoxycorticosterone by injection or by subcutaneous implantation of pellets resulted in a threefold increase in kallikrein excretion after 10-30 days ( P <0.01). Low-sodium intake produced a twofold increase in kallikrein excretion after 2 and 4 weeks ( P <0.01). Urine volume and blood pressure were normal and unchanged throughout the study. Sodium excretion was unaltered by deoxycorticosterone but was essentially zero during low-sodium intake. Adrenalectomized rats excreted less than half the kallikrein of shamoperated control rats ( P <0.01). These data show a direct relationship between mineralocorticoids and kallikrein excretion and suggest that mineralocorticoids are a primary factor regulating the urinary excretion of kallikrein in rats.

Renin suppression by DOC and NaCl in the rat.

Renin suppression by DOC and NaCl in the rat.