Acute salt loading and cardiotonic steroids in resistant hypertension

Emelyanov, I.; Konradi, Alexandra; Lakatta, Edward G.; Федорова, О. В.; Bagrov, Alexei Y.

doi:10.1016/bs.ctm.2019.01.005

Cited by 4 publications

(9 citation statements)

References 23 publications

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“…Experimental studies revealed that both acute [ 23 , 36 ] and chronic [ 24 ] sodium chloride load may stimulate the synthesis of marinobufagenin. Similar observations were made in humans; however, limited data are available and they include small groups of patients with normal or moderately elevated blood pressure [ 37 , 38 , 39 ] or with resistant hypertension [ 40 ]. Moreover, it was postulated that increased MBG secretion after high sodium load is an attempt to compensate for impaired pressure-natriuresis in the animal model of salt-sensitivity [ 25 ].…”

Section: Discussionmentioning

confidence: 74%

“…Parallel to this observation, other authors noted that high-salt intake (for 4 weeks) induced a small but significant elevation in plasma MBG concentration, whereas urinary MBG excretion has not changed [ 39 ]. Only one study, performed in 34 patients with resistant hypertension, showed that acute salt loading for 60 min via intravenous infusion of 1 L of 0.9% NaCl resulted in the increase of plasma MBG concentration immediately after the salt loading [ 40 ]. In contrast to our observation all patients received a thiazide diuretic and salt loading resulted in a substantial BP rise.…”

Section: Discussionmentioning

confidence: 99%

“…As was previously pointed out by other investigators, the overall plasma MBG level depends upon the adrenal marinobufagenin secretion, diurnal variations typical for steroid hormones and the supposed kidney role in local production, and metabolism and storage of MBG [ 25 , 37 ]. Furthermore, in all previously reported studies except one [ 40 ] the condition defined as high salt-intake was induced through increased salt ingestion for 6 days or for 4 weeks, whereas in our cohort we used intravenous sodium chloride load, in the amount of 2 L infused over 4 h. Notably, when we evaluated hematocrit values we found that in salt-sensitive individuals, hematocrit values were lower 24 h after sodium load than immediately after the infusion of sodium chloride, where the opposite occurs in salt-insensitive patients. One can assume that this observation in the salt-sensitive sub-group was a consequence of sodium and water retention.…”

Section: Discussionmentioning

confidence: 99%

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The Effects of Short-Term Changes in Sodium Intake on Plasma Marinobufagenin Levels in Patients with Primary Salt-Sensitive and Salt-Insensitive Hypertension

Łabno-Kirszniok¹,

Kujawa-Szewieczek²,

Wiȩcek³

et al. 2021

Nutrients

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Increased marinobufagenin (MBG) synthesis has been suggested in response to high dietary salt intake. The aim of this study was to determine the effects of short-term changes in sodium intake on plasma MBG levels in patients with primary salt-sensitive and salt-insensitive hypertension. In total, 51 patients with primary hypertension were evaluated during acute sodium restriction and sodium loading. Plasma or serum concentrations of MBG, natriuretic pro-peptides, aldosterone, sodium, potassium, as well as hematocrit (Hct) value, plasma renin activity (PRA) and urinary sodium and potassium excretion were measured. Ambulatory blood pressure monitoring (ABPM) and echocardiography were performed at baseline. In salt-sensitive patients with primary hypertension plasma MBG correlated positively with diastolic blood pressure (ABPM) and serum NT-proANP concentration at baseline and with serum NT-proANP concentration after dietary sodium restriction. In this subgroup plasma MBG concentration decreased during sodium restriction, and a parallel increase of PRA was observed. Acute salt loading further decreased plasma MBG concentration in salt-sensitive subjects in contrast to salt insensitive patients. No correlation was found between plasma MBG concentration and left ventricular mass index. In conclusion, in salt-sensitive hypertensive patients plasma MBG concentration correlates with 24-h diastolic blood pressure and dietary sodium restriction reduces plasma MBG levels. Decreased MBG secretion in response to acute salt loading may play an important role in the pathogenesis of salt sensitivity.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Effects of Short-Term Changes in Sodium Intake on Plasma Marinobufagenin Levels in Patients with Primary Salt-Sensitive and Salt-Insensitive Hypertension

Łabno-Kirszniok¹,

Kujawa-Szewieczek²,

Wiȩcek³

et al. 2021

Nutrients

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“… 4 , 7 In these subjects, excessive production of marinobufagenin occurs to override sodium retention, but marinobufagenin exhibits a maladaptive effect, inhibits NKA in the vascular sarcolemma, and raises BP. 7 , 8 Previously it was demonstrated that plasma levels of marinobufagenin in humans and in rodent models range from 0.1 to 2 nmol/L, that is, physiological marinobufagenin level, and it is higher in preeclampsia, chronic kidney disease, and salt‐sensitive hypertension. 7 , 8 , 9 , 10 , 11 , 12 …”

mentioning

confidence: 99%

“… 7 , 8 Previously it was demonstrated that plasma levels of marinobufagenin in humans and in rodent models range from 0.1 to 2 nmol/L, that is, physiological marinobufagenin level, and it is higher in preeclampsia, chronic kidney disease, and salt‐sensitive hypertension. 7 , 8 , 9 , 10 , 11 , 12 …”

mentioning

confidence: 99%

Silencing of PKG1 Gene Mimics Effect of Aging and Sensitizes Rat Vascular Smooth Muscle Cells to Cardiotonic Steroids: Impact on Fibrosis and Salt Sensitivity

Федорова

Shilova

Zernetkina

et al. 2023

JAHA

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Background Marinobufagenin, NKA (Na/K‐ATPase) inhibitor, causes vasoconstriction and induces fibrosis via inhibition of Fli1 (Friend leukemia integration‐1), a negative regulator of collagen synthesis. In vascular smooth muscle cells (VSMC), ANP (atrial natriuretic peptide), via a cGMP/PKG1 (protein kinase G1)‐dependent mechanism, reduces NKA sensitivity to marinobufagenin. We hypothesized that VSMC from old rats, due to downregulation of ANP/cGMP/PKG‐dependent signaling, would exhibit heightened sensitivity to the profibrotic effect of marinobufagenin. Methods and Results Cultured VSMC from the young (3‐month‐old) and old (24‐month‐old) male Sprague–Dawley rats and young VSMC with silenced PKG1 gene were treated with 1 nmol/L ANP, or with 1 nmol/L marinobufagenin, or with a combination of ANP and marinobufagenin. Collagen‐1, Fli1, and PKG1 levels were assessed by Western blotting analyses. Vascular PKG1 and Fli1 levels in the old rats were reduced compared with their young counterparts. ANP prevented inhibition of vascular NKA by marinobufagenin in young VSMC but not in old VSMC. In VSMC from the young rats, marinobufagenin induced downregulation of Fli1 and an increase in collagen‐1 level, whereas ANP blocked this effect. Silencing of the PKG1 gene in young VSMC resulted in a reduction in levels of PKG1 and Fli1; marinobufagenin additionally reduced Fli1 and increased collagen‐1 level, and ANP failed to oppose these marinobufagenin effects, similar to VSMC from the old rats with the age‐associated reduction in PKG1. Conclusions Age‐associated reduction in vascular PKG1 and the resultant decline in cGMP signaling lead to the loss of the ability of ANP to oppose marinobufagenin‐induced inhibition of NKA and fibrosis development. Silencing of the PKG1 gene mimicked these effects of aging.

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Mechanisms providing effects of cardiotonic steroids in mammalian cells with special attention to blood cells

Poluektov,

Lopina,

Strelkova

et al. 2023

Preprint

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Cardiotonic steroids (CTS) are a group of steroid compounds derived from certain plants and animals. CTS are selective inhibitors of Na,K-ATPase, so for a long time they were widely used for medical purposes to treat heart failure and some other diseases. However, over time, doctors gradually began to refuse this group of drugs due to their narrow therapeutic range and a number of serious side effects. However, in parallel with the rise and fall of interest in CTS as a drug, interest in them as a single class of high-affinity Na,K-ATPase inhibitors has only increased. Numerous data on the effect of CTS on signaling cascades and cell viability made impelling a search for a rationale for the existence of such a subtle biological regulator. A large number of studies devoted to the potential use of CTS in the treatment of neurodegenerative, oncological, immune and other diseases "revitalized" the already "written off" group of the drugs. If initially the role of exogenous (mainly plant origin) CTS was studied, then by the 90s of the XX century the study of the role of endogenous CTS and their regulatory effects became a popular trend in biology and physiology. The role of endogenous CTS was studied in details in the pathogenesis of cardiovascular diseases [1]. A large number of researchers have unanimously stated that endogenous CTS are very complex regulators of the development of pathological processes; however, the exact cause-and-effect relationship that would unambiguously explain the processes of synthesis, utilization, and the role of endogenous CTS has not yet been established. The effects of CTS in the frame of various regulatory schemes have been described, but the predominant number of studies was devoted to arterial hypertension, heart and renal failure, cancer [2–4], aging [5,6], and neuroinflammation. The effects of both endo- and exogenous CTS on blood cells and have been studied to a much lesser extent.

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Acute salt loading and cardiotonic steroids in resistant hypertension

Cited by 4 publications

References 23 publications

The Effects of Short-Term Changes in Sodium Intake on Plasma Marinobufagenin Levels in Patients with Primary Salt-Sensitive and Salt-Insensitive Hypertension

The Effects of Short-Term Changes in Sodium Intake on Plasma Marinobufagenin Levels in Patients with Primary Salt-Sensitive and Salt-Insensitive Hypertension

Silencing of PKG1 Gene Mimics Effect of Aging and Sensitizes Rat Vascular Smooth Muscle Cells to Cardiotonic Steroids: Impact on Fibrosis and Salt Sensitivity

Mechanisms providing effects of cardiotonic steroids in mammalian cells with special attention to blood cells

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