Digitalis-like pregnanes. Cardiac and renal effects of a glycoside of 14β-hydroxyprogesterone

1988 ◽  
Vol 66 (11) ◽  
pp. 1420-1424 ◽  
Author(s):  
J. F. Templeton ◽  
V. P. Sashi Kumar ◽  
D. Bose ◽  
D. D. Smyth ◽  
R. S. Kim ◽  
...  

The synthesis of the glucoside, 3β-[(β-D-glucopyranosyl)oxy]-14-hydroxy-14β-pregn-4-en-20-one, a 14β-hydroxyprogesterone glucoside (14β-OHP-glu), is described. This compound has an IC50 of 1 μM in a [3H]ouabain binding assay, and is about 10 times more potent than the aglycone. Like 14β-hydroxyprogesterone, the glucoside enhances contractility of isolated cardiac muscle. 14β-OHP-glu or ouabain, when infused at comparable doses into the renal artery of the anesthetized rat, markedly increases urine volume. Whereas ouabain significantly enhances urinary potassium excretion with little or no effect on sodium excretion, 14β-OHP-glu promotes a marked natriuresis with no significant effect on potassium excretion.

1965 ◽  
Vol 209 (6) ◽  
pp. 1187-1192 ◽  
Author(s):  
George A. Bray

Cold exposure causes rats to increase their urine output. This increase in urine output was found to occur in 5- to 8-day cycles with peak urine volumes three or more times the volumes prior to exposure to the cold. Cycles in urine volume occurred on a constant electrolyte intake and in animals receiving exogenous Pitressin. The peaks in urine volume were accompanied by a threefold increase in the variability of sodium excretion but not potassium excretion. The increase in urine volume which occurred at the same time in all rats in a group began at night and continued through the following day. These data have been discussed in the light of a possible mechanism controlling sodium intake with water intake and electrolyte excretion.


1990 ◽  
Vol 258 (5) ◽  
pp. F1401-F1408 ◽  
Author(s):  
D. R. Martin ◽  
J. B. Pevahouse ◽  
D. J. Trigg ◽  
D. L. Vesely ◽  
J. E. Buerkert

The present investigation was designed to determine whether peptides derived from the NH(2)-terminal portion of the 126-amino acid prohormone (pro) of atrial natriuretic factor (ANF) have natriuretic and diuretic properties similar to ANF. Three peptides consisting of amino acids 1-30 [(proANF-(1-30)], 31-67 [proANF-(31-67)], and 79-98 (proANF-(79-98)] of the ANF prohormone were tested and compared with the COOH-terminus peptide (ANF) with respect to their ability to increase urine volume, urine sodium and potassium excretion, and glomerular filtration rate (GFR) in anesthetized Munich-Wistar rats. Each of these peptides except proANF-(79-98) caused a significant diuresis (P less than 0.05) when infused at their respective 100 ng.kg body wt-1.min-1 concentrations for 120 min. ProANFs-(1-30), (31-67), (79-98), and (99-126) (ANF) increased sodium excretion by 231, 973, 167, and 1,405%, respectively. The fractional excretion of sodium compared with control was significant at P less than 0.05, P less than 0.01, and P less than 0.05 for proANFs (1-30), (31-67), and (99-126), respectively. ProANF-(79-98) did not significantly increase the fractional excretion of sodium, but it was the only peptide from the NH(2)-terminus of the prohormone that significantly increased the fractional excretion of potassium's ProANF-(31-67) did not increase urinary potassium excretion. ProANF-(1-30), (79-98), and ANF significantly (P less than 0.05) increased urinary potassium excretion. None of these peptides significantly enhanced GFR. In conclusion, three peptides from the NH(2)-terminus of the ANF prohormone as well as ANF (the COOH-terminus) have either natriuretic, kaliuretic, and/or diuretic properties, but the respective ability of each of these peptides to produce these effects varies considerably.


2021 ◽  
Author(s):  
Mohamed idrissi ◽  
Naima Saeid ◽  
Samir Mounach ◽  
Hicham El Berri ◽  
Ayoub Al Jawaldah ◽  
...  

Abstract Background: Excessive sodium (Na) intake and low potassium (K) intake are associated with adverse cardiovascular health outcomes. Morocco lacks data on actual Na and K intake in adults. The aim of this study was to estimate the mean intake of Na and K in a Moroccan population of adults using the 24-h urinary excretion and to examine their association with blood pressure (BP). Methods: A total of 371 adults, who participated in the urinary validation sub-study of the STEP-wise Survey-Morocco-2017-2018, have complete data on demographic, anthropometric and blood pressure and have provided a valid 24-h urine collection according to the standard protocol of the World Health Organization (WHO). Results: The mean 24-h urinary sodium excretion was 2794 mg (SD, 1394) and the median was 2550 mg (IQR, 1780-3726). The mean 24-h urinary potassium excretion was 1898 mg (SD, 1044) and the median was 1640 mg (IQR, 1170-2410). Sodium excretion was between 3000 and 5000 mg/day in 31% of participants, < 3000 mg/day in 64%, and > 5000 mg/day in only 5%. No significant association of urinary sodium or potassium with blood pressure was found. Conclusion: Sodium intake in the studied population of Moroccan adults was higher than WHO recommendation and was comparable to levels reported in countries from Eastern Mediterranean Region. The vast majority of participants had a sodium intake < 5000 mg/day, with only 5% were above this level. Potassium intake was in the range of 1000 to 3000 mg/day. Within these ranges, there was no association between sodium or potassium intake and blood pressure. This information is crucial to help implement the national strategy to reduce sodium intake as a cost-effective intervention to prevent chronic disease in Morocco.


1967 ◽  
Vol 47 (1) ◽  
pp. 39-46 ◽  
Author(s):  
V. V. E. St. Omer ◽  
W. K. Roberts

Balance studies were conducted with heifers weighing between 210–258 kg to determine effects of different dietary potassium levels, 156.6 (low), 439.4 (medium) and 1,086.8 (high) meq upon nutrient utilization. The low potassium ration produced an average negative potassium balance of 25.2 meq daily, while the other rations produced positive potassium balances. Urinary potassium excretion was markedly affected by potassium level while fecal potassium excretion was much less affected: in general, the higher the potassium intake, the higher the urinary and fecal potassium excretions. All heifers were in positive sodium balance and dietary level of potassium did not significantly influence either urinary or fecal excretion of sodium. Nitrogen balance was not significantly affected by treatment, but urinary ammonia excretion was significantly (P < 0.01) higher when the low potassium ration was fed. Water consumption and urine volume were significantly (P < 0.01) higher for the heifers fed high potassium, but water balance was not affected. Apparent digestibilities of energy, dry matter, nitrogen, crude fiber and ether extract were not significantly affected by treatment.Serum potassium levels were lower (P < 0.05) and phosphorus higher (P < 0.05) in heifers receiving the low than in heifers receiving the high level of potassium. Serum concentrations of sodium, chloride, calcium and magnesium were not significantly affected by dietary potassium.From the data, the potassium requirement for maintenance of the heifers was estimated to be 133 meq potassium daily per 100 kg body weight.


1997 ◽  
Vol 272 (3) ◽  
pp. F333-F338 ◽  
Author(s):  
E. K. Jackson ◽  
P. Li

The purpose of this study was to determine whether leptin influences renal function. Increasing doses (0.3, 1, 3, 10, and 30 microg/min; 30 min per dose) of human leptin (h-leptin) infused into the renal artery of anesthetized rats caused a twofold increase (P < 0.01) in urine volume (UV), sodium excretion rate (U(Na)V), and the ratio of U(Na)V to potassium excretion rate (U(K)V) from the ipsilateral kidney but had no effect on arterial blood pressure, renal blood flow, glomerular filtration rate, or U(K)V. Mouse leptin was inactive in the rat. In a second study, a single dose of h-leptin (30 microg/min) infused into the renal artery caused a significant twofold increase in UV and U(Na)V from the ipsilateral but not contralateral kidney and revealed a time lag (approximately 1.5 h) in the measurable response. In a third study, single doses of h-leptin were infused into the renal artery of four groups of rats (0.3, 1, 3, and 10 microg/min) for 140 min. The ratio of U(Na)V to U(K)V from the ipsilateral kidney was significantly increased by all doses of h-leptin. We conclude that h-leptin may function as a potassium-sparing diuretic/natriuretic factor.


1978 ◽  
Vol 235 (3) ◽  
pp. R175-R180 ◽  
Author(s):  
F. M. Sulzman ◽  
C. A. Fuller ◽  
L. G. Hiles ◽  
M. C. Moore-Ede

The relative contributions of light-dark (LD) cycles and feeding (EF) cycles in providing temporal information to the circadian time-keeping system were examined in chair-acclimatized squirrel monkeys (Saimiri sciureus). The circadian rhythms of drinking, colonic temperature, urine volume, and urinary potassium excretion were measured with the LD and EF cycles providing either conflicting phases or periods. In conflicting phase experiments, animals were exposed to 24-h LD cycles consisting of 12 h of 600 lx followed by 12 h of less than 1 ls and concurrent 24-h EF cycles in which the animals ate for 3 h and then fasted for 21 h. One group had food available at the beginning and a second group at the end of the light period. In conflicting period experiments, monkeys were exposed to 23-h LD cycles (LD 11.5:11.5) and 24-h EF cycles (EF 3:21). Analysis of the rhythms showed that both phase and period information were conveyed to the drinking and urinary rhythms by the EF cycle, and to the temperature rhythm by the LD cycle.


1987 ◽  
Vol 72 (4) ◽  
pp. 449-454 ◽  
Author(s):  
L. F. O. Obika ◽  
M. MARIN-GREZ

1. The effect of amiloride administration on the urinary kallikrein response to the injection or continuous infusion of frusemide in normal Sprague–Dawley rats was investigated. 2. Injections of frusemide induced repeatedly an increase in urinary kallikrein excretion. This effect was suppressed by amiloride. Amiloride also blocked the response to mannitol injection. A continuous infusion of frusemide lasting 100 min also induced an increase in urinary kallikrein excretion which persisted throughout the experiment. This response was completely blocked by the injection of amiloride. 3. Urinary kallikrein excretion was directly and positively related to urine volume and urinary sodium excretion before and after amiloride injection. The regression lines had markedly decreased slopes after amiloride administration. The urinary kallikrein excretion was also positively related to the urine volume and urinary sodium excretion when frusemide was continuously infused. However, these relationships were abolished after amiloride injection. 4. In both the injection and the infusion experiments, there was a direct relationship of urinary kallikrein excretion to urinary potassium excretion. Although this relationship persisted after amiloride injection, the regression line was shifted to the left. 5. The suppression of the kallikrein stimulating effect of frusemide by the sodium channel blocker amiloride indicates that distal tubule sodium re-absorption is the triggering factor in urinary kallikrein excretion. The study suggests that the mechanism involved in the release of kallikrein by the distal tubular cells is linked to the renal mechanism affected by amiloride.


2000 ◽  
Vol 78 (2) ◽  
pp. 93-99 ◽  
Author(s):  
Angela Bischoff ◽  
Martin C Michel

Neuropeptide Y (NPY) is an established modulator of renal function. Although NPY reduces renal blood flow and does not alter glomerular filtration rate, it enhances diuresis and natriuresis. Although initial studies on natriuresis did not detect kaliuresis, we now report that a retrospective analysis of previous studies regarding natriuresis demonstrates NPY-induced kaliuresis under several experimental conditions. Kaliuresis was observed despite a marked reduction in urinary potassium concentrations, which may explain why it has not been noted in some initial studies. In a direct comparison of NPY-induced kaliuresis and natriuresis, both effects were slow in onset (requiring >45 min to develop fully) and blocked by the cyclooxygenase inhibitor indomethacin. While natriuresis occurred solely via a Y5 receptor, kaliuresis involved a Y1 receptor and an additional receptor subtype, possibly Y2. The L-type Ca2+ entry blocker nifedipine abolished natriuresis but did not inhibit kaliuresis. A combination of experiments with the bradykinin B2 receptor antagonist icatibant, the angiotensin II receptor antagonist losartan, and the converting enzyme inhibitor ramiprilat revealed that NPY-induced natriuresis involves bradykinin while kaliuresis involves angiotensin II. We conclude that NPY-induced kaliuresis is much less pronounced than natriuresis and is mediated by distinct mechanisms.Key words: neuropeptide Y, potassium excretion, sodium excretion, angiotensin II, cyclooxygenase.


1992 ◽  
Vol 70 (5) ◽  
pp. 723-727 ◽  
Author(s):  
D. D. Smyth ◽  
J. F. Templeton ◽  
V. P. Sashi Kumar ◽  
Y. Yan ◽  
W. Widajewicz ◽  
...  

The synthesis of 17α-acetoxy-3β-[(β-D-glucopyranosyl)oxy]-6α-methylpregn-4-en-20-one, the glucoside of medroxyprogesterone acetate (MPA-glu), is described. MPA-glu and 14-amino-20β-hydroxy-3β-[(α-L-rhamnopyranosyl)oxy]-5β,14β-pregnane (LND 623), pregnane glycosides that bind to the digitalis receptor, and digoxin, a cardiac glycoside, were infused intravenously into the anesthetized guinea pig. Each of the three steroids significantly enhanced urinary volume and sodium excretion without affecting blood pressure and creatinine clearance. Potassium excretion was markedly enhanced by digoxin but unaffected by MPA-glu or LND 623. These observations conform to previous work that demonstrated, in the rat, potassium-sparing diuresis by the glucoside of 14β-hydroxyprogesterone, a cardiotonic pregnane. There is a dissociation between potency to inhibit [3H]ouabain binding and the extra ATPase actions of the digitaloid pregnanes.Key words: pregnanes, cardiac glycosides, diuretic, LND 623, medroxyprogesterone acetate.


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