Digitaloid pregnanes promote potassium-sparing diuresis in the guinea pig

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.

1987 ◽  
Vol 65 (12) ◽  
pp. 2428-2432 ◽  
Author(s):  
J. Michael Wyss ◽  
Wanida Sripairojthikoon ◽  
Suzanne Oparil

In previous experiments we have demonstrated that the renal nerves play a significant role in all genetic and (or) induced models of hypertension that we have studied. The current experiments extended this research by investigating the contribution of the renal nerves to hypertension in the Dahl NaCl-sensitive rat. This was investigated by assessing the effect of bilateral phenol renal denervation carried out prior to initiation of a high NaCl (8% NaCl) diet. In two separate studies, renal denervation did not affect systolic blood pressure in either Dahl NaCl-sensitive rats or their normotensive counterparts, Dahl NaCl-resistant rats. Further, denervation did not increase absolute urinary sodium excretion, percent urinary sodium excretion, urinary volume output, or food or water intake; nor did it differentially alter creatinine clearance or body weight. Denervation was verified at the termination of each study by a greater than 80% depletion of renal noradrenaline stores. These results indicate that the renal nerves do not provide a major contribution to hypertension in the Dahl NaCl-sensitive rat.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaofu Du ◽  
Le Fang ◽  
Jianwei Xu ◽  
Xiangyu Chen ◽  
Yamin Bai ◽  
...  

AbstractThe direction and magnitude of the association between sodium and potassium excretion and blood pressure (BP) may differ depending on the characteristics of the study participant or the intake assessment method. Our objective was to assess the relationship between BP, hypertension and 24-h urinary sodium and potassium excretion among Chinese adults. A total of 1424 provincially representative Chinese residents aged 18 to 69 years participated in a cross-sectional survey in 2017 that included demographic data, physical measurements and 24-h urine collection. In this study, the average 24-h urinary sodium and potassium excretion and sodium-to-potassium ratio were 3811.4 mg/day, 1449.3 mg/day, and 4.9, respectively. After multivariable adjustment, each 1000 mg difference in 24-h urinary sodium excretion was significantly associated with systolic BP (0.64 mm Hg; 95% confidence interval [CI] 0.05–1.24) and diastolic BP (0.45 mm Hg; 95% CI 0.08–0.81), and each 1000 mg difference in 24-h urinary potassium excretion was inversely associated with systolic BP (− 3.07 mm Hg; 95% CI − 4.57 to − 1.57) and diastolic BP (− 0.94 mm Hg; 95% CI − 1.87 to − 0.02). The sodium-to-potassium ratio was significantly associated with systolic BP (0.78 mm Hg; 95% CI 0.42–1.13) and diastolic BP (0.31 mm Hg; 95% CI 0.10–0.53) per 1-unit increase. These associations were mainly driven by the hypertensive group. Those with a sodium intake above about 4900 mg/24 h or with a potassium intake below about 1000 mg/24 h had a higher risk of hypertension. At higher but not lower levels of 24-h urinary sodium excretion, potassium can better blunt the sodium-BP relationship. The adjusted odds ratios (ORs) of hypertension in the highest quartile compared with the lowest quartile of excretion were 0.54 (95% CI 0.35–0.84) for potassium and 1.71 (95% CI 1.16–2.51) for the sodium-to-potassium ratio, while the corresponding OR for sodium was not significant (OR, 1.28; 95% CI 0.83–1.98). Our results showed that the sodium intake was significantly associated with BP among hypertensive patients and the inverse association between potassium intake and BP was stronger and involved a larger fraction of the population, especially those with a potassium intake below 1000 mg/24 h should probably increase their potassium intake.


1980 ◽  
Vol 59 (s6) ◽  
pp. 161s-164s ◽  
Author(s):  
P. S. Parfrey ◽  
P. Wright ◽  
J. M. Ledingham

1. The diurnal excretion of sodium and potassium was observed in young people, with and without a genetic predisposition to hypertension, both in the presence and absence of psychological stress. 2. In the absence of stress, the normal day/night sodium excretion ratio was reversed in the children of hypertensive parents. This was significantly less than day/night sodium excretion in children of normotensive parents. A similar finding was observed for day/night potassium excretion. 3. There was a significant negative correlation between systolic blood pressure and day/night sodium excretion in children of hypertensive parents but not in children of normotensive parents. 4. After the mental stress of a University examination day/night sodium reverted to normal in children of hypertensive parents.


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.


1983 ◽  
Vol 245 (5) ◽  
pp. R633-R636
Author(s):  
T. Sugai ◽  
Y. Nakagawa ◽  
K. Takeda ◽  
S. Imai

To know the role played by the kidney in the genesis of deoxycorticosterone acetate (DOCA)-saline hypertension, the arterial pressure-urinary output (AP-UO) relationship was compared in unanesthetized, unrestrained uninephrectomized (1-K) control and normal Wistar-Imamichi (W-I) rats according to the method of Norman et al. [Am. J. Physiol. 234 (Regulatory Integrative Comp. Physiol. 3): R98-R103, 1973]. The gradient of AP-UO relationship was slightly decreased in 1-K control rats compared with that in W-I rats. However, the AP-UO relationship of DOCA-saline hypertensive rats underwent only a parallel shift to higher blood pressure ranges compared with that of 1-K control rats. There was no significant change in the urinary volume, urinary sodium excretion, and urinary osmolarity. Furthermore, the AP-UO relationship was shifted back to the lower pressure range under the influence of hydralazine, a preferential renal arteriolar dilator, suggesting that constriction of the renal artery caused the rise of the arterial pressure in DOCA-saline hypertensive rats.


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.


1991 ◽  
Vol 260 (5) ◽  
pp. F663-F669 ◽  
Author(s):  
J. E. Hall ◽  
M. W. Brands ◽  
H. L. Mizelle ◽  
C. A. Gaillard ◽  
D. A. Hildebrandt

Hyperinsulinemia has been postulated to link obesity and hypertension via the antinatriuretic actions of insulin. The main goal of this study was to quantitate the importance of the direct intrarenal actions of insulin, independent of systemic effects, in altering blood pressure and renal function. This was accomplished by determining the responses to chronic intrarenal insulin infusion in uninephrectomized, chronically instrumented conscious dogs maintained on a 74 meq/day sodium intake. Insulin was infused at rates calculated to raise intrarenal, but not systemic, insulin to levels similar to those observed in obese hypertensive dogs. Intrarenal insulin infusion (0.6 mU.kg-1.min-1) for 7 days caused transient decreases in sodium excretion but no significant changes in potassium excretion. Mean arterial pressure did not change during 7 days of insulin infusion, averaging 93 +/- 4 mmHg during control and 93 +/- 3 mmHg during insulin infusion. Intrarenal insulin caused small increases in GFR but no significant changes in effective renal plasma flow or renal vascular resistance. These results demonstrate that insulin causes transient decreases in sodium excretion, but chronic intrarenal hyperinsulinemia does not elevate blood pressure in normal dogs. Additional factors other than the direct sodium-retaining effects of insulin may be important in raising blood pressure in obesity-associated hypertension.


1985 ◽  
Vol 248 (4) ◽  
pp. R495-R500 ◽  
Author(s):  
R. H. Freeman ◽  
J. O. Davis ◽  
R. C. Vari

Constriction of the thoracic inferior vena cava to decrease venous return and atrial filling markedly elevates plasma renin activity (PRA) and plasma aldosterone concentration (PAC) and produces chronic sodium retention and ascites in the dog. Infusion of a synthetic atrial natriuretic factor into conscious dogs with caval constriction and ascites at doses of 175 and 350 ng X kg-1 X min-1 for 30 min each produced striking increases (P less than 0.05) in creatinine clearance, diuresis, and kaliuresis but failed to increase urinary sodium excretion. Infusions of atrial natriuretic factor at these doses into conscious normal dogs, however, produced a striking increase in sodium excretion from 41 +/- 14 and 55 +/- 19 mu eq/min to 150 +/- 58 and 181 +/- 49 mu eq/min (P less than 0.05 for both values). Creatinine clearance and urine flow also increased in these normal dogs, but potassium excretion remained unchanged during the infusion periods. Atrial natriuretic factor produced parallel suppression (P less than 0.05) of the elevated levels of PRA and PAC in the caval dogs but failed to significantly decrease either PRA or PAC in the normal animals. Arterial pressure, heart rate, and PAH clearance were unchanged in both groups of dogs during infusion of atrial natriuretic factor. These results suggest that the pattern of renal electrolyte excretion elicited in response to the acute infusion of atrial natriuretic factor is dependent, at least partially, on the preexisting status of the renal tubules to facilitate sodium reabsorption and potassium excretion. The results also are consistent with the concept that atrial natriuretic factor might function to tonically inhibit the renin-angiotensin-aldosterone system.


1972 ◽  
Vol 42 (6) ◽  
pp. 711-723 ◽  
Author(s):  
R. Wilkinson ◽  
J. A. Luetscher ◽  
A. J. Dowdy ◽  
C. Gonzales ◽  
G. W. Nokes

1. A group of eight patients with advanced renal failure, and a creatinine clearance of 3·8–24 ml/min, were subjected to sodium loading and sodium depletion. 2. With sodium loading there was a consistent increase in blood pressure (0·01 < P <0·02), an increase in creatinine clearance that was significantly related to changes in mean arterial pressure (r = +0·3, 001 < P < 0·02); an increase in urinary sodium excretion that was closely correlated with changes in creatinine clearance (r = +0·82, P < 0·001); a decrease in fractional reabsorption of filtered sodium that was inversely proportional to creatinine clearance (r = −0·63, 0·05< P < 0·1). 3. Fractional reabsorption of filtered sodium was proportional to creatinine clearance both in the sodium-loaded (r = +0·86, 0·001 < P < 0·01) and sodium-depleted states (r = +0·92, 0·001 < P < 0·01). 4. Urinary aldosterone excretion and plasma renin activity consistently increased with sodium depletion, the percentage increases of the two being significantly related (r = +0·95, P < 0·001). 5. The results suggest that excretion of a sodium load in uraemia may be effected in part as the result of a raised blood pressure that elevates the glomerular filtration rate; by increasing the peritubular capillary pressure this may be responsible for the observed decrease in reabsorption of filtered sodium. The responsiveness of glomerular filtration rate to blood pressure changes suggests a decrease in afferent arteriolar tone that may account for the increased sodium excretion per nephron which occurs even in uraemic patients without hypertension. 6. It is suggested that aldosterone may continue to play an important regulatory role in sodium homeostasis in uraemia and that renin concentrations are the major determinants of aldosterone production in uraemia.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Paula Moliterno ◽  
Ramón Álvarez-Vaz ◽  
Matias Pécora ◽  
Leonella Luzardo ◽  
Luciana Borgarello ◽  
...  

Many public health policies in Latin America target an optimized sodium and potassium intake. The aims of this study were to assess the sodium and potassium intake using 24-hour urinary analysis and to study their association with blood pressure in a Uruguayan population cohort using cluster analysis. A total of 149 participants (aged 20–85 years) were included in the study, and office blood pressure, anthropometric measurements, biochemical parameters in the blood, and 24-hour urine samples were obtained. The overall mean sodium and potassium excretion was 152.9 ± 57.3 mmol/day (8.9 ± 3.4 g/day of salt) and 55.4 ± 19.6 mmol/day, respectively. The average office systolic/diastolic blood pressure was 124.6 ± 16.7/79.3 ± 9.9 mmHg. Three compact spherical clusters were defined in untreated participants based on predetermined attributes, including blood pressure, age, and sodium and potassium excretion. The major characteristics of the three clusters were (1) high systolic blood pressure and moderate sodium excretion, (2) moderate systolic blood pressure and very high sodium excretion, and (3) low systolic blood pressure and low sodium excretion. Participants in cluster three had systolic blood pressure values that were 23.9 mmHg (95% confidence interval: −29.5 to −1.84) lower than those in cluster one. Participants in cluster two had blood pressure levels similar to those in cluster one (P = 0.32) and worse metabolic profiles than those in cluster one and three (P < 0.05). None of the clusters showed high blood pressure levels and high sodium excretion. No linear association was found between blood pressure and urinary sodium excretion (r < 0.14; P > 0.47). An effect of sodium and potassium intake on blood pressure levels was not found at the population level using regression or cluster analysis.


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