Mineralocorticoid escape during kallikrein inhibition

1986 ◽  
Vol 70 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Axel Overlack ◽  
Evita Bäcker-Kreutz ◽  
Christa Ressel ◽  
Hans-Michael Müller ◽  
Rainer Kolloch ◽  
...  
Keyword(s):  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Potassium Excretion ◽  
Sodium Retention ◽  
Metabolic Study ◽  
Kinin System ◽  
Important Mediator ◽  
Pg E2 ◽  
Kallikrein Kinin System ◽  
Sodium And Potassium

1. Kinins have been considered to be involved in the escape from the sodium retaining effects of mineralocorticoids. In a metabolic study in rats, the importance of the kallikrein-kinin system for sodium and potassium excretion was evaluated by aprotinin-induced kallikrein inhibition under basal conditions and during DOCA administration. 2. Kallikrein inhibition was accompanied by a transient sodium retention. The escape from the sodium retaining effect of DOCA was not affected. However, the DOCA-induced potassium loss was enhanced. 3. Kallikrein inhibition decreased urinary prostaglandin (PG) E2 and prevented the DOCA-induced rise in PGE2. Plasma renin activity was stimulated after 10 days of aprotinin administration. 4. The kallikrein-kinin system is not an important mediator of the escape phenomenon but it may play a role in the regulation of sodium and potassium excretion.

Involvement of Prostaglandins in the Actions of Captopril

1982 ◽  
Vol 63 (s8) ◽  
pp. 265s-267s ◽  
Author(s):  
H. Witzgall ◽  
B. Scherer ◽  
P. C. Weber
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Plasma Renin Activity ◽  
Urine Volume ◽  
Plasma Renin ◽  
Potassium Excretion ◽  
Arterial Blood ◽  
Pg E2 ◽  
Excretion Rates ◽  
Sodium And Potassium

1. Haemodynamic and hormonal actions of 100 mg of captopril (SQ 14 225) orally were tested in 12 healthy volunteers with and without indomethacin pretreatment. 2. Without indomethacin, mean arterial blood pressure was reduced at 30 and 60 min after captopril (P < 0.02). Heart rate did not change. Plasma renin activity (PRA) increased (P < 0.002), and plasma and urinary aldosterone as well as plasma 18-hydroxycorticosterone (18- OH-B) decreased after captopril (P < 0.02). Prostaglandin (PG) E2, kallikrein, urine volume, sodium and potassium excretion rates remained constant after captopril. 3. Under indomethacin pretreatment, blood pressure was reduced to a smaller degree at 30 and 60 min after captopril (P < 0.05). Heart rate was constantly lower than without indomethacin (P < 0.05). Indomethacin decreased basal PGE2 and kallikrein excretion (P < 0.02) and reduced basal PRA as well as the increase of PRA after captopril (P < 0.05). Basal mineralocorticoid levels were significantly lower than without indomethacin. Aldosterone did not decrease further after captopril, and 18-OH-B fell only slightly. 4. The results suggest that prostaglandins may be involved in the haemodynamic and hormonal actions of captopril.

Effects of modulation of renal kallikrein-kinin system in the nephrotic syndrome

1990 ◽  
Vol 258 (5) ◽  
pp. F1237-F1244
Author(s):  
F. N. Hutchison ◽  
V. I. Martin
Keyword(s):  
Blood Pressure ◽  
Enzyme Inhibitors ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Ang Ii ◽  
Converting Enzyme Inhibitors ◽  
Kinin System ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System

Albuminuria (UAlbV) can be reduced by converting-enzyme inhibitors (CEI), but the hormonal mechanism responsible for this effect has not previously been defined. Since CEI increase kinin activity as well as reduce angiotensin II (ANG II) activity, experiments were performed to determine the effect of isolated alterations in kinin and ANG II metabolism on UAlbV in rats with passive Heymann pephritis. Phosphoramidon was used to potentiate kinin activity without altering ANG II synthesis. Aprotinin was utilized in combination with the CEI, enalapril, to prevent the increase in kinin activity caused by CEI. UAlbV and the fractional renal clearance of albumin (FCAlb) decreased significantly after either phosphoramidon or enalapril, although only enalapril reduced blood pressure. Glomerular filtration rate (GFR) was not affected by either drug. Phosphoramidon did not affect plasma renin activity (PRA) or the pressor response to angiotensin I (ANG I), indicating that ANG II synthesis was not altered. Aprotinin prevented the reduction in UAlbV and FCAlb produced by CEI but not the hypotension, elevated PRA, or ANG I pressor blockade produced by CEI. Aprotinin alone had no effect on UAlbV, GFR, PRA, or blood pressure. UAlbV can be reduced by increasing kinin activity by a mechanism that is not dependent on suppression of ANG II activity or reduction in GFR or blood pressure. CEI may reduce proteinuria as a result of their action on the kallikrein-kinin system rather than on the renin-angiotensin system.

scholarly journals Reduction of plasma renin activity by inhibition of the fatty acid cyclooxygenase in human subjects: independence of sodium retention.

1979 ◽  
Vol 44 (6) ◽  
pp. 781-787 ◽  
Author(s):  
J C Frölich ◽  
J W Hollifield ◽  
A M Michelakis ◽  
B S Vesper ◽  
J P Wilson ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Plasma Renin Activity ◽  
Human Subjects ◽  
Plasma Renin ◽  
Renin Activity ◽  
Sodium Retention

The Effect of Mineralocorticoid Administration on Urine Free Dopamine in Man

1980 ◽  
Vol 58 (1) ◽  
pp. 77-82 ◽  
Author(s):  
N. S. Oates ◽  
C. M. Perkins ◽  
M. R. Lee
Keyword(s):  
Plasma Renin Activity ◽  
Chloride Concentration ◽  
Plasma Renin ◽  
Normal Subjects ◽  
Sodium Concentration ◽  
Renin Activity ◽  
Potassium Intake ◽  
Metabolic Conditions ◽  
Renal Dopamine ◽  
Sodium And Potassium

1. Five normal subjects were studied under metabolic conditions on a controlled sodium and potassium intake. 2. Plasma and urine free dopamine concentrations were measured in these subjects before, during and after 5 days administration of fludrocortisone (0·2 mg twice daily). 3. Urine free dopamine showed a tendency to fall during the early phase of fludrocortisone administration and then rose towards normal. 4. In a patient with primary hyperaldosteronism there was no evidence of increased renal production of dopamine. Urine dopamine fell when plasma renin activity rose as a result of spironolactone administration (200 mg three times a day for 5 days). 5. If renal dopamine has a role in mineralocorticoid ‘escape’ then it may be permissive only. The mechanisms of control of dopamine production could include tubular sodium concentration, tubular chloride concentration and intrarenal renin activity.

Tissue kallikrein deficiency and renovascular hypertension in the mouse

2009 ◽  
Vol 296 (5) ◽  
pp. R1385-R1391 ◽  
Author(s):  
Violaine Griol-Charhbili ◽  
Laurent Sabbah ◽  
Juliana Colucci ◽  
Marie-Pascale Vincent ◽  
Véronique Baudrie ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Left Ventricular ◽  
Tissue Kallikrein ◽  
Kinin System ◽  
Kidney Blood Flow ◽  
Kallikrein Kinin System

The kallikrein kinin system (KKS) is involved in arterial and renal functions. It may have an antihypertensive effect in both essential and secondary forms of hypertension. The role of the KKS in the development of two-kidneys, one-clip (2K1C) hypertension, a high-renin model, was investigated in mice rendered deficient in tissue kallikrein (TK) and kinins by TK gene inactivation (TK−/−) and in their wild-type littermates (TK+/+). Four weeks after clipping the renal artery, blood flow was reduced in the clipped kidney (2K1C-TK+/+: −90%, 2K1C-TK−/−: −93% vs. sham-operated mice), and the kidney mass had also decreased (2K1C-TK+/+: −65%, 2K1C-TK−/−: −66%), whereas in the unclipped kidney, blood flow (2K1C-TK+/+: +19%, 2K1C-TK−/−: +17%) and kidney mass (2K1C-TK+/+: +32%, 2K1C-TK−/−: +30%) had both increased. The plasma renin concentration (2K1C-TK+/+: +78%, 2K1C-TK−/−: +65%) and renal renin content of the clipped kidney (2K1C-TK+/+: +58%, 2K1C-TK−/−: +65%) had increased significantly. There was no difference for these parameters between 2K1C-TK+/+ and 2K1C-TK−/− mice. Blood pressure monitored by telemetry and by plethysmography, rose immediately after clipping in both genotypes, and reached similar levels (2K1C-TK+/+: +24%, 2K1C-TK−/−: +21%). 2K1C-TK+/+ and 2K1C-TK−/− mice developed similar concentric left ventricular hypertrophy (+24% and +17%, respectively) with normal cardiac function. These findings suggest that in the context of chronic unilateral reduction in renal blood flow, TK and kinins do not influence the trophicity of kidneys, the synthesis and secretion of renin, blood pressure increase, and cardiac remodeling due to renin angiotensin system activation.

Involvement of sodium retention hormones during rehydration in humans

1988 ◽  
Vol 65 (1) ◽  
pp. 332-336 ◽  
Author(s):  
H. Nose ◽  
G. W. Mack ◽  
X. R. Shi ◽  
E. R. Nadel
Keyword(s):  
Body Weight ◽  
Plasma Renin Activity ◽  
Plasma Volume ◽  
Tap Water ◽  
Control Level ◽  
Plasma Renin ◽  
The Body ◽  
Sodium Retention ◽  
Adult Males ◽  
Nacl Solution

We investigated the relation between involuntary dehydration and the mechanisms affecting Na+ retention in the body, focusing on the renin-angiotensin-aldosterone system. Six adult males were dehydrated to 2.3% of their body weight by an exercise-heat regimen, followed by rehydration (180 min) with tap water (H2O-R) or 0.45% NaCl solution (Na-R). We measured plasma renin activity (PRA) and aldosterone levels (PA) before dehydration (control), after dehydration, and at 60, 120, and 180 min of rehydration. During the 3-h rehydration period, subjects, restored 51% of the water lost during H2O-R and 71% during Na-R (P less than 0.05). Plasma volume was reduced by an average of 4.5% after dehydration. After 180 min of rehydration, plasma volume restoration during Na-R was to 174% of that lost, and during H2O-R it was to 78% of that lost. We found significant correlations between the change in plasma volume and PRA (r = -0.70, P less than 0.001) and between PRA and PA (r = 0.71, P less than 0.001). In both recovery conditions, PRA increased significantly after dehydration (P less than 0.05) and decreased almost to the control level by 180 min of rehydration, at which time the plasma volume deficit was restored. The change in PA paralleled that in PRA. The rate of sodium excretion was correlated with PA levels in both groups (r = -0.58, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Sodium, potassium and chloride utilization by rats given various inorganic anions

1991 ◽  
Vol 66 (3) ◽  
pp. 523-532 ◽  
Author(s):  
Susan M. Kaup ◽  
Alison R. Behling ◽  
J. L. Greger
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Basal Diet ◽  
Renin Activity ◽  
Sprague Dawley ◽  
Sodium Potassium ◽  
Sprague Dawley Rats ◽  
Blood Pressures ◽  
Sodium And Potassium

The purpose of the present studies was to examine the effect of ingestion of sodium and potassium salts of various fixed anions on blood pressure, and to assess interactions among electrolytes. In the first study, Sprague-Dawley rats fed on purified diets supplemented with Na salts of chloride, sulphate, bisulphate, carbonate and bicarbonate for 7 weeks developed higher blood pressures than rats fed on the basal diet. In a second study, rats fed on Na or K salts of HSO4, HCO3 or Cl had higher blood pressures than rats fed on the basal diet. Blood pressure measurements were not correlated with plasma volume, plasma renin activity, or plasma atrial natriuretic peptide concentrations at 7 weeks. Plasma renin activity was depressed in rats fed on supplemental Na and even more in rats fed on supplemental K salts rather than the basal diet. Generally, rats fed on supplemental Na excreted Na in urine and absorbed Na in the gut more efficiently than rats fed on the basal diet or diets supplemented with K, but the anions fed also altered Na absorption and excretion. In a third study, rats fed on diets supplemented with any Cl salt, but especially KCI, absorbed K more efficiently than those fed on the basal diet. In studies 1 and 2, the efficiency of urinary excretion of K was greatest when HCO3 and CO3 salts were fed and least when HSO4 salts were fed. Despite large variations in the efficiency of absorption and excretion of Na and K, tissue levels of the electrolytes remained constant.

Hypertension after ending captopril administration: pathogenesis in 2-kidney, 1-clip rat

1984 ◽  
Vol 247 (6) ◽  
pp. H946-H951
Author(s):  
J. M. DeForrest ◽  
J. S. Creekmore ◽  
R. A. Ferrone
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Effect ◽  
Severe Hypertension ◽  
Peripheral Resistance ◽  
Plasma Renin ◽  
Kinin System ◽  
Series Of Experiments ◽  
Sympathetic Nervous ◽  
Kallikrein Kinin System ◽  
Prostaglandin System

We have previously shown that continuous captopril administration prevents hypertension from developing in the two-kidney, one-clip (2K, 1C) rat. The present investigation was designed to determine the mechanism(s) producing the hypertension. In one series of experiments captopril prevented pressure from increasing during an 8-wk treatment period. Relative to the last day of treatment, mean arterial pressure and total peripheral resistance (TPR) were increased and cardiac output was unchanged at 3, 7, and 28 days after captopril cessation. Plasma renin activity (PRA) was unchanged 3, 7, and 14 days after captopril cessation but was elevated at 28, 49, and 56 days after captopril cessation only in 2K, 1C rats with severe hypertension (systolic blood pressure greater than 180 mmHg). Guanethidine (45 mg/kg po, bid) did not prevent the development of 2K, 1C hypertension but did prevent the hypertension from developing after cessation of captopril. Blockade of the prostaglandin system with indomethacin (5 mg/kg + 50 micrograms X kg-1 X min-1) and of the kallikrein-kinin system with aprotinin (25,000 KIU + 150 KIU X kg-1 X min-1) for 2 h had no effect on captopril's antihypertensive effect. Additionally, no change in sodium or water balance was observed after captopril cessation. Taken together these data demonstrate that hypertension after captopril cessation is due to an increase in TPR. Additionally, the rise in TPR is due to both the sympathetic nervous and the renin-angiotensin systems since both systems must be functional before pressure rises.

Sodium Balance, Fluid Homeostasis and the Renin–Aldosterone System during the Prolonged Exercise of Hill Walking

1982 ◽  
Vol 62 (6) ◽  
pp. 595-604 ◽  
Author(s):  
J. S. Milledge ◽  
E. I. Bryson ◽  
D. M. Catley ◽  
R. Hesp ◽  
N. Luff ◽  
...  
Keyword(s):  
Plasma Renin Activity ◽  
Extracellular Space ◽  
Prolonged Exercise ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Renin Activity ◽  
Sodium Retention ◽  
Plasma Aldosterone Concentration ◽  
Fluid Homeostasis ◽  
Exercise Period

1. The effect of 5 consecutive days of hill walking on electrolyte balance, fluid homeostasis, plasma renin activity and plasma aldosterone concentration was studied in five male subjects. 2. The 5-day exercise period was preceded by a 4-day control period and followed by a 4-day recovery period. Throughout the 13-day study subjects ate a fixed diet. 3. After 5 days of exercise subjects had retained a mean of 264 mmol (sd 85) of sodium. Plasma sodium concentration remained constant at 142.0 mmol/l (sd 5.4). This indicates an expansion of the extracellular space by 1.84 litres. 4. By the end of the exercise period there was a positive water balance of about 0.9 litre. Thus there was a net movement of 0.94 litre of fluid from the intracellular to the extracellular space. 5. Packed cell volume decreased from a mean of 43.5% to 37.9% after 5 days of exercise, indicating that about 0.9 litre of the extracellular fluid entered the vascular compartment. The remaining fluid may be responsible for the significant increase in lower leg volume. 6. During the exercise period plasma aldosterone concentration and plasma renin activity rose, and there was a highly significant correlation between these values and the sodium retention. There was also a significant correlation between sodium retention and the increase in leg volume, which suggests that oedema may be the result of prolonged exercise of this type.

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