Myocardial cross-bridge kinetics in transition to failure in Dahl salt-sensitive rats

2001 ◽  
Vol 281 (3) ◽  
pp. H1390-H1396 ◽  
Author(s):  
Daniel T. McCurdy ◽  
Bradley M. Palmer ◽  
David W. Maughan ◽  
Martin M. LeWinter
Keyword(s):  
Mechanical Performance ◽  
Dynamic Stiffness ◽  
Calcium Sensitivity ◽  
Left Ventricular ◽  
Isometric Tension ◽  
High Salt Diet ◽  
Salt Diet ◽  
Cross Bridge ◽  
Cross Bridges

The role of altered cross-bridge kinetics during the transition from cardiac hypertrophy to failure is poorly defined. We examined this in Dahl salt-sensitive (DS) rats, which develop hypertrophy and failure when fed a high-salt diet (HS). DS rats fed a low-salt diet were controls. Serial echocardiography disclosed compensated hypertrophy at 6 wk of HS, followed by progressive dilatation and impaired function. Mechanical properties of skinned left ventricular papillary muscle strips were analyzed at 6 wk of HS and then during failure (12 wk HS) by applying small amplitude (0.125%) length perturbations over a range of calcium concentrations. No differences in isometric tension-calcium relations or cross-bridge cycling kinetics or mechanical function were found at 6 wk. In contrast, 12 wk HS strips exhibited increased calcium sensitivity of isometric tension, decreased frequency of minimal dynamic stiffness, and a decreased range of frequencies over which cross bridges produce work and power. Thus the transition from hypertrophy to heart failure in DS rats is characterized by major changes in cross-bridge cycling kinetics and mechanical performance.

scholarly journals Metabolic Syndrome and Salt-Sensitive Hypertension in Polygenic Obese TALLYHO/JngJ Mice: Role of Na/K-ATPase Signaling

2019 ◽  
Vol 20 (14) ◽  
pp. 3495 ◽  
Author(s):  
Yanling Yan ◽  
Jiayan Wang ◽  
Muhammad A. Chaudhry ◽  
Ying Nie ◽  
Shuyan Sun ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Significant Rise ◽  
Protein Carbonylation ◽  
High Salt ◽  
Kidney Cortex ◽  
High Salt Diet ◽  
Salt Diet ◽  
Salt Sensitive Hypertension

We have demonstrated that Na/K-ATPase acts as a receptor for reactive oxygen species (ROS), regulating renal Na+ handling and blood pressure. TALLYHO/JngJ (TH) mice are believed to mimic the state of obesity in humans with a polygenic background of type 2 diabetes. This present work is to investigate the role of Na/K-ATPase signaling in TH mice, focusing on susceptibility to hypertension due to chronic excess salt ingestion. Age-matched male TH and the control C57BL/6J (B6) mice were fed either normal diet or high salt diet (HS: 2, 4, and 8% NaCl) to construct the renal function curve. Na/K-ATPase signaling including c-Src and ERK1/2 phosphorylation, as well as protein carbonylation (a commonly used marker for enhanced ROS production), were assessed in the kidney cortex tissues by Western blot. Urinary and plasma Na+ levels were measured by flame photometry. When compared to B6 mice, TH mice developed salt-sensitive hypertension and responded to a high salt diet with a significant rise in systolic blood pressure indicative of a blunted pressure-natriuresis relationship. These findings were evidenced by a decrease in total and fractional Na+ excretion and a right-shifted renal function curve with a reduced slope. This salt-sensitive hypertension correlated with changes in the Na/K-ATPase signaling. Specifically, Na/K-ATPase signaling was not able to be stimulated by HS due to the activated baseline protein carbonylation, phosphorylation of c-Src and ERK1/2. These findings support the emerging view that Na/K-ATPase signaling contributes to metabolic disease and suggest that malfunction of the Na/K-ATPase signaling may promote the development of salt-sensitive hypertension in obesity. The increased basal level of renal Na/K-ATPase-dependent redox signaling may be responsible for the development of salt-sensitive hypertension in polygenic obese TH mice.

scholarly journals Phosphate has dual roles in cross-bridge kinetics in rabbit psoas single myofibrils

2021 ◽  
Vol 153 (3) ◽  
Author(s):  
Masataka Kawai ◽  
Robert Stehle ◽  
Gabriele Pfitzer ◽  
Bogdan Iorga
Keyword(s):  
Rate Constants ◽  
Striated Muscle ◽  
Intrinsic Rate ◽  
Isometric Tension ◽  
Force Generation ◽  
Skinned Fibers ◽  
Sinusoidal Analysis ◽  
Rabbit Psoas ◽  
Cross Bridge

In this study, we aimed to study the role of inorganic phosphate (Pi) in the production of oscillatory work and cross-bridge (CB) kinetics of striated muscle. We applied small-amplitude sinusoidal length oscillations to rabbit psoas single myofibrils and muscle fibers, and the resulting force responses were analyzed during maximal Ca2+ activation (pCa 4.65) at 15°C. Three exponential processes, A, B, and C, were identified from the tension transients, which were studied as functions of Pi concentration ([Pi]). In myofibrils, we found that process C, corresponding to phase 2 of step analysis during isometric contraction, is almost a perfect single exponential function compared with skinned fibers, which exhibit distributed rate constants, as described previously. The [Pi] dependence of the apparent rate constants 2πb and 2πc, and that of isometric tension, was studied to characterize the force generation and Pi release steps in the CB cycle, as well as the inhibitory effect of Pi. In contrast to skinned fibers, Pi does not accumulate in the core of myofibrils, allowing sinusoidal analysis to be performed nearly at [Pi] = 0. Process B disappeared as [Pi] approached 0 mM in myofibrils, indicating the significance of the role of Pi rebinding to CBs in the production of oscillatory work (process B). Our results also suggest that Pi competitively inhibits ATP binding to CBs, with an inhibitory dissociation constant of ∼2.6 mM. Finally, we found that the sinusoidal waveform of tension is mostly distorted by second harmonics and that this distortion is closely correlated with production of oscillatory work, indicating that the mechanism of generating force is intrinsically nonlinear. A nonlinear force generation mechanism suggests that the length-dependent intrinsic rate constant is asymmetric upon stretch and release and that there may be a ratchet mechanism involved in the CB cycle.

Effects of a chronic high-salt diet on large artery structure: role of endogenous bradykinin

1998 ◽  
Vol 274 (5) ◽  
pp. H1423-H1428 ◽  
Author(s):  
Chohreh Partovian ◽  
Athanase Benetos ◽  
Jean-Pierre Pommiès ◽  
Willy Mischler ◽  
Michel E. Safar
Keyword(s):  
Blood Pressure ◽  
High Salt ◽  
Large Artery ◽  
High Salt Diet ◽  
Salt Diet ◽  
Wky Rats ◽  
Arterial Blood ◽  
Arterial Structure ◽  
Hoe 140

Bradykinin activity could explain the blood pressure increase during NaCl loading in hypertensive animals, but its contribution on vascular structure was not evaluated. We determined cardiac mass and large artery structure after a chronic, 4-mo, high-salt diet in combination with bradykinin B2-receptor blockade by Hoe-140. Four-week-old rats were divided into eight groups according to strain [spontaneously hypertensive rats (SHR) vs. Wistar-Kyoto (WKY) rats], diet (0.4 vs. 7% NaCl), and treatment (Hoe-140 vs. placebo). In WKY rats, a high-salt diet significantly increased intra-arterial blood pressure with minor changes in arterial structure independently of Hoe-140. In SHR, blood pressure remained stable but 1) the high-salt diet was significantly associated with cardiovascular hypertrophy and increased arterial elastin and collagen, and 2) Hoe-140 alone induced carotid hypertrophy. A high-salt diet plus Hoe-140 acted synergistically on carotid hypertrophy and elastin content in SHR, suggesting that the role of endogenous bradykinin on arterial structure was amplified in the presence of a high-salt diet.

scholarly journals Time course of decompensation after angiotensin II and high-salt diet in Balb/CJ mice suggests pulmonary hypertension-induced cardiorenal syndrome

2019 ◽  
Vol 316 (5) ◽  
pp. R563-R570 ◽  
Author(s):  
Mediha Becirovic-Agic ◽  
Sofia Jönsson ◽  
Maria K. Tveitarås ◽  
Trude Skogstrand ◽  
Tine V. Karlsen ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Angiotensin Ii ◽  
Cardiac Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
High Salt ◽  
Ang Ii ◽  
Salt Treatment ◽  
High Salt Diet ◽  
Salt Diet

The genetic background of a mouse strain determines its susceptibility to disease. C57BL/6J and Balb/CJ are two widely used inbred mouse strains that we found react dramatically differently to angiotensin II and high-salt diet (ANG II + Salt). Balb/CJ show increased mortality associated with anuria and edema formation while C57BL/6J develop arterial hypertension but do not decompensate and die. Clinical symptoms of heart failure in Balb/CJ mice gave the hypothesis that ANG II + Salt impairs cardiac function and induces cardiac remodeling in male Balb/CJ but not in male C57BL/6J mice. To test this hypothesis, we measured cardiac function using echocardiography before treatment and every day for 7 days during treatment with ANG II + Salt. Interestingly, pulsed wave Doppler of pulmonary artery flow indicated increased pulmonary vascular resistance and right ventricle systolic pressure in Balb/CJ mice, already 24 h after ANG II + Salt treatment was started. In addition, Balb/CJ mice showed abnormal diastolic filling indicated by reduced early and late filling and increased isovolumic relaxation time. Furthermore, Balb/CJ exhibited lower cardiac output compared with C57BL/6J even though they retained more sodium and water, as assessed using metabolic cages. Left posterior wall thickness increased during ANG II + Salt treatment but did not differ between the strains. In conclusion, ANG II + Salt treatment causes early restriction of pulmonary flow and reduced left ventricular filling and cardiac output in Balb/CJ, which results in fluid retention and peripheral edema. This makes Balb/CJ a potential model to study the adaptive capacity of the heart for identifying new disease mechanisms and drug targets.

scholarly journals Role of Endothelin B Receptors in Enhancing Endothelium-Dependent Nitric Oxide–Mediated Vascular Relaxation During High Salt Diet

Hypertension ◽  
2001 ◽  
Vol 37 (2) ◽  
pp. 516-523 ◽  
Author(s):  
Jena B. Giardina ◽  
GaChavis M. Green ◽  
Anna N. Rinewalt ◽  
Joey P. Granger ◽  
Raouf A. Khalil
Keyword(s):  
Nitric Oxide ◽  
High Salt ◽  
Vascular Relaxation ◽  
High Salt Diet ◽  
Salt Diet ◽  
Endothelin B

scholarly journals Role of central nervous system aldosterone synthase and mineralocorticoid receptors in salt-induced hypertension in Dahl salt-sensitive rats

2009 ◽  
Vol 296 (4) ◽  
pp. R994-R1000 ◽  
Author(s):  
Bing S. Huang ◽  
Roselyn A. White ◽  
Arco Y. Jeng ◽  
Frans H. H. Leenen
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Aldosterone Synthase ◽  
High Salt Intake ◽  
Induced Hypertension ◽  
Synthase Inhibitor ◽  
The Brain

In Dahl salt-sensitive (S) rats, high salt intake increases cerebrospinal fluid (CSF) Na+ concentration ([Na+]) and blood pressure (BP). Intracerebroventricular (ICV) infusion of a mineralocorticoid receptor (MR) blocker prevents the hypertension. To assess the role of aldosterone locally produced in the brain, we evaluated the effects of chronic central blockade with the aldosterone synthase inhibitor FAD286 and the MR blocker spironolactone on changes in aldosterone and corticosterone content in the hypothalamus and the increase in CSF [Na+] and hypertension induced by high salt intake in Dahl S rats. After 4 wk of high salt intake, plasma aldosterone and corticosterone were not changed, but hypothalamic aldosterone increased by ∼35% and corticosterone tended to increase in Dahl S rats, whereas both steroids decreased by ∼65% in Dahl salt-resistant rats. In Dahl S rats fed the high-salt diet, ICV infusion of FAD286 or spironolactone did not affect the increase in CSF [Na+]. ICV infusion of FAD286 prevented the increase in hypothalamic aldosterone and 30 mmHg of the 50-mmHg BP increase induced by high salt intake. ICV infusion of spironolactone fully prevented the salt-induced hypertension. These results suggest that, in Dahl S rats, high salt intake increases aldosterone synthesis in the hypothalamus and aldosterone acts as the main MR agonist activating central pathways contributing to salt-induced hypertension.

Effects of high-salt diet on CYP450-4A ω-hydroxylase expression and active tone in mesenteric resistance arteries

2005 ◽  
Vol 288 (4) ◽  
pp. H1557-H1565 ◽  
Author(s):  
Jingli Wang ◽  
Richard J. Roman ◽  
John R. Falck ◽  
Lourdes de la Cruz ◽  
Julian H. Lombard
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
Resistance Arteries ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Dietary Salt Intake ◽  
Vasoconstrictor Response ◽  
Cytochrome P 450

This study investigated the role of changes in the expression of the cytochrome P-450 4A (CYP450-4A) enzymes that produce 20-hydroxyeicosatetraenoic acid (20-HETE) in modulating the responses of rat mesenteric resistance arteries to norepinephrine (NE) and reduced Po2 after short-term (3-day) changes in dietary salt intake. The CYP450-4A2, -4A3, and -4A8 isoforms were all detected by RT-PCR in arteries obtained from rats fed a high-salt (HS, 4% NaCl) diet, whereas only the CYP450-4A3 isoform was detected in vessels from rats fed a low-salt (LS, 0.4% NaCl) diet. Expression of the 51-kDa CYP450-4A protein was significantly increased by a HS diet. Inhibiting 20-HETE synthesis with 30 μM N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) reduced the vasoconstrictor response to NE in arteries obtained from rats fed either a LS or HS diet, but NE sensitivity after DDMS treatment was significantly lower in vessels from rats on a HS diet. DDMS treatment also restored the vasodilator response to reduced Po2 that was impaired in arteries from rats on a HS diet. These findings suggest that 1) a HS diet increases the expression of CYP450-4A enzymes in the mesenteric vasculature, 2) 20-HETE contributes to the vasoconstrictor response to NE in mesenteric resistance arteries, 3) the contribution of 20-HETE to the vasoconstrictor response to NE is greater in rats fed a HS diet than in rats fed a LS diet, and 4) upregulation of the production of 20-HETE contributes to the impaired dilation of mesenteric resistance arteries in response to hypoxia in rats fed a HS diet.

scholarly journals Fructose plus High-Salt Diet in Early Life Results in Salt-Sensitive Cardiovascular Changes in Mature Male Sprague Dawley Rats

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3129
Author(s):  
Peter E. Levanovich ◽  
Charles S. Chung ◽  
Dragana Komnenov ◽  
Noreen F. Rossi
Keyword(s):  
Phase I ◽  
Left Ventricular ◽  
High Salt ◽  
Male Rats ◽  
Phase Iii ◽  
Lv Function ◽  
Sprague Dawley ◽  
High Salt Diet ◽  
Salt Diet ◽  
Sprague Dawley Rats

Fructose and salt intake remain high, particularly in adolescents and young adults. The present studies were designed to evaluate the impact of high fructose and/or salt during pre- and early adolescence on salt sensitivity, blood pressure, arterial compliance, and left ventricular (LV) function in maturity. Male 5-week-old Sprague Dawley rats were studied over three 3-week phases (Phases I, II, and III). Two reference groups received either 20% glucose + 0.4% NaCl (GCS-GCS) or 20% fructose + 4% NaCl (FHS-FHS) throughout this study. The two test groups ingested fructose + 0.4% NaCl (FCS) or FHS during Phase I, then GCS in Phase II, and were then challenged with 20% glucose + 4% NaCl (GHS) in Phase III: FCS-GHS and FHS-GHS, respectively. Compared with GCS-GCS, systolic and mean pressures were significantly higher at the end of Phase III in all groups fed fructose during Phase I. Aortic pulse wave velocity (PWV) was elevated at the end of Phase I in FHS-GHS and FHS-FHS (vs. GCS-GCS). At the end of Phase III, PWV and renal resistive index were higher in FHS-GHS and FHS-FHS vs. GCS-GCS. Diastolic, but not systolic, LV function was impaired in the FHS-GHS and FHS-FHS but not FCS-FHS rats. Consumption of 20% fructose by male rats during adolescence results in salt-sensitive hypertension in maturity. When ingested with a high-salt diet during this early plastic phase, dietary fructose also predisposes to vascular stiffening and LV diastolic dysfunction in later life.

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