Gene deletion of P2Y4 receptor lowers exercise capacity and reduces myocardial hypertrophy with swimming exercise

2012 ◽  
Vol 303 (7) ◽  
pp. H835-H843 ◽  
Author(s):  
Michael Horckmans ◽  
Elvira Léon-Gómez ◽  
Bernard Robaye ◽  
Jean-Luc Balligand ◽  
Jean-Marie Boeynaems ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Hypertrophy ◽  
Open Field ◽  
Exercise Capacity ◽  
Prolonged Exercise ◽  
Receptor Expression ◽  
Tail Suspension ◽  
Wild Type ◽  
Exercise Induced

Nucleotides released within the heart under pathological conditions can be involved in cardioprotection or cardiac fibrosis through the activation purinergic P2Y2 and P2Y6 receptors, respectively. We previously demonstrated that adult P2Y4-null mice display a microcardia phenotype related to a cardiac angiogenic defect. To evaluate the functional consequences of this defect, we performed here a combination of cardiac monitoring and exercise tests. We investigated the exercise capacity of P2Y4 wild-type and P2Y4-null mice in forced swimming and running tests. Analysis of their stress, locomotion, and resignation was realized in open field, black and white box, and tail suspension experiments. Exercise-induced cardiac hypertrophy was evaluated after repeated and prolonged exercise in P2Y4 wild-type and P2Y4-null hearts. We showed that P2Y4-null mice have a lower exercise capacity in both swimming and treadmill tests. This was not related to decreased motivation or increased stress, since open field, white and black box, and mouse tail suspension tests gave comparable results in P2Y4 wild-type and P2Y4-null mice. Heart rate and blood pressure rose normally in P2Y4-null swimming mice equipped with a telemetric implant. On the contrary, we observed a delayed recovery of postexercise blood pressure after exercise in P2Y4-null mice. The heart rate increment in response to catecholamines was also similar in P2Y4 wild-type and P2Y4-null implanted mice, which is consistent with a similar level of cardiac β-receptor expression. Interestingly, the heart of P2Y4-null mice displayed a reduced sympathetic innervation associated with a decreased norepinephrine level. We also demonstrated that exercise-induced cardiac hypertrophy was lower in P2Y4-null mice after repeated and prolonged exercise. This was associated with a lower increase in cardiomyocyte size and microvessel density. In conclusion, besides its role in cardiac development, P2Y4 receptor could constitute an important regulator of acute and chronic response to exercise.

scholarly journals Salt sensitivity of blood pressure in NKCC1-deficient mice

2008 ◽  
Vol 295 (4) ◽  
pp. F1230-F1238 ◽  
Author(s):  
Soo Mi Kim ◽  
Christoph Eisner ◽  
Robert Faulhaber-Walter ◽  
Diane Mizel ◽  
Susan M. Wall ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Wheel Running ◽  
Plasma Renin ◽  
Pressure Change ◽  
Standard Diet ◽  
Wild Type ◽  
Vascular Effects ◽  
Arterial Blood ◽  
Deficient Mice

NKCC1 is a widely expressed isoform of the Na-2Cl-K cotransporter that mediates several direct and indirect vascular effects and regulates expression and release of renin. In this study, we used NKCC1-deficient (NKCC1−/−) and wild-type (WT) mice to assess day/night differences of blood pressure (BP), locomotor activity, and renin release and to study the effects of high (8%) or low (0.03%) dietary NaCl intake on BP, activity, and the renin/aldosterone system. On a standard diet, 24-h mean arterial blood pressure (MAP) and heart rate determined by radiotelemetry, and their day/night differences, were not different in NKCC1−/− and WT mice. Spontaneous and wheel-running activities in the active night phase were lower in NKCC1−/− than WT mice. In NKCC1−/− mice on a high-NaCl diet, MAP increased by 10 mmHg in the night without changes in heart rate. In contrast, there was no salt-dependent blood pressure change in WT mice. MAP reductions by hydralazine (1 mg/kg) or isoproterenol (10 μg/mouse) were significantly greater in NKCC1−/− than WT mice. Plasma renin (PRC; ng ANG I·ml−1·h−1) and aldosterone (aldo; pg/ml) concentrations were higher in NKCC1−/− than WT mice (PRC: 3,745 ± 377 vs. 1,245 ± 364; aldo: 763 ± 136 vs. 327 ± 98). Hyperreninism and hyperaldosteronism were found in NKCC1−/− mice during both day and night. High Na suppressed PRC and aldosterone in both NKCC1−/− and WT mice, whereas a low-Na diet increased PRC and aldosterone in WT but not NKCC1−/− mice. We conclude that 24-h MAP and MAP circadian rhythms do not differ between NKCC1−/− and WT mice on a standard diet, probably reflecting a balance between anti- and prohypertensive factors, but that blood pressure of NKCC1−/− mice is more sensitive to increases and decreases of Na intake.

Parameters to Be Measured during Exercise

2018 ◽  
pp. 82-105
Author(s):  
Gregory S. Thomas ◽  
Myrvin H. Ellestad
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Myocardial Ischemia ◽  
Oxygen Uptake ◽  
Exercise Duration ◽  
Metabolic Equivalents ◽  
Include Blood Pressure ◽  
Electrocardiographic Changes ◽  
Health And Disease ◽  
Exercise Induced

The chapter Parameters to be Measured During Exercise reviews the physiologic changes with exercise which indicate health and disease. Key parameters include blood pressure, heart rate, electrocardiographic changes, exercise duration, maximum oxygen uptake (VO2max), and anaerobic threshold. An in-depth review and consensus estimate is provided to estimate metabolic equivalents (METs) achieved based on exercise duration on the Bruce and Ellestad protocols. Use of bipolar leads for detection of exercise induced myocardial ischemia is discussed, typified by CM5 which captures up to 90% of patients with an electrocardiographic manifestation of ischemia. Changes in murmurs that occur with exercise are reviewed; walk-through angina and chronotropic incompetence.

scholarly journals Deficiency of T-type Ca2+ channels Cav3.1 and Cav3.2 has no effect on angiotensin II-induced hypertension but differential effect on plasma aldosterone in mice

2019 ◽  
Vol 317 (2) ◽  
pp. F254-F263
Author(s):  
Anne D. Thuesen ◽  
Stine H. Finsen ◽  
Louise L. Rasmussen ◽  
Ditte C. Andersen ◽  
Boye L. Jensen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Mineralocorticoid Receptor ◽  
Plasma Aldosterone ◽  
Receptor Blocker ◽  
Ang Ii ◽  
Induced Hypertension

T-type Ca2+ channel Cav3.1 promotes microvessel contraction ex vivo. It was hypothesized that in vivo, functional deletion of Cav3.1, but not Cav3.2, protects mice against angiotensin II (ANG II)-induced hypertension. Mean arterial blood pressure (MAP) and heart rate were measured continuously with chronically indwelling catheters during infusion of ANG II (30 ng·kg−1·min−1, 7 days) in wild-type (WT), Cav3.1−/−, and Cav3.2−/− mice. Plasma aldosterone and renin concentrations were measured by radioimmunoassays. In a separate series, WT mice were infused with ANG II (100 ng·kg−1·min−1) with and without the mineralocorticoid receptor blocker canrenoate. Cav3.1−/− and Cav3.2−/− mice exhibited no baseline difference in MAP compared with WT mice, but day-night variation was blunted in both Cav3.1 and Cav3.2−/− mice. ANG II increased significantly MAP in WT, Cav3.1−/−, and Cav3.2−/− mice with no differences between genotypes. Heart rate was significantly lower in Cav3.1−/− and Cav3.2−/− mice compared with control mice. After ANG II infusion, plasma aldosterone concentration was significantly lower in Cav3.1−/− compared with Cav3.2−/− mice. In response to ANG II, fibrosis was observed in heart sections from both WT and Cav3.1−/− mice and while cardiac atrial natriuretic peptide mRNA was similar, the brain natriuretic peptide mRNA increase was mitigated in Cav3.1−/− mice ANG II at 100 ng/kg yielded elevated pressure and an increased heart weight-to-body weight ratio in WT mice. Cardiac hypertrophy, but not hypertension, was prevented by the mineralocorticoid receptor blocker canrenoate. In conclusion, T-type channels Cav3.1and Cav3.2 do not contribute to baseline blood pressure levels and ANG II-induced hypertension. Cav3.1, but not Cav3.2, contributes to aldosterone secretion. Aldosterone promotes cardiac hypertrophy during hypertension.

scholarly journals Contribution of BKCa channels to local metabolic coronary vasodilation: effects of metabolic syndrome

2010 ◽  
Vol 298 (3) ◽  
pp. H966-H973 ◽  
Author(s):  
Léna Borbouse ◽  
Gregory M. Dick ◽  
Gregory A. Payne ◽  
Brittany D. Payne ◽  
Mark C. Svendsen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Heart Rate ◽  
Atherogenic Diet ◽  
Bkca Channels ◽  
Selective Blockade ◽  
Before And After ◽  
Lactate Uptake ◽  
Exercise Induced ◽  
The Relationship

This investigation was designed to examine the hypothesis that impaired function of coronary microvascular large-conductance Ca2+-activated K+ (BKCa) channels in metabolic syndrome (MetS) significantly attenuates the balance between myocardial oxygen delivery and metabolism at rest and during exercise-induced increases in myocardial oxygen consumption (MV̇o2). Studies were conducted in conscious, chronically instrumented Ossabaw swine fed a normal maintenance diet (11% kcal from fat) or an excess calorie atherogenic diet (43% kcal from fat, 2% cholesterol, 20% kcal from fructose) that induces many common features of MetS. Data were collected under baseline/resting conditions and during graded treadmill exercise before and after selective blockade of BKCa channels with penitrem A (10 μg/kg iv). We found that the exercise-induced increases in blood pressure were significantly elevated in MetS swine. No differences in baseline cardiac function or heart rate were noted. Induction of MetS produced a parallel downward shift in the relationship between coronary venous Po2 and MV̇o2 ( P < 0.001) that was accompanied by a marked release of lactate (negative lactate uptake) as MV̇o2 was increased with exercise ( P < 0.005). Inhibition of BKCa channels with penitrem A did not significantly affect blood pressure, heart rate, or the relationship between coronary venous Po2 and MV̇o2 in lean or MetS swine. These data indicate that BKCa channels are not required for local metabolic control of coronary blood flow under physiological (lean) or pathophysiological (MetS) conditions. Therefore, diminished function of BKCa channels does not contribute to the impairment of myocardial oxygen-supply demand balance in MetS.

Comparative β-Adrenoreceptor-Blocking Effects and Pharmacokinetics of Propranolol and Pindolol in Hypertensive Africans

1979 ◽  
Vol 57 (s5) ◽  
pp. 393s-396s ◽  
Author(s):  
L. A. Salako ◽  
A. O. Falase ◽  
A. Fadeke Aderounmu
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Systolic Blood Pressure ◽  
Diastolic Pressure ◽  
Exercise Heart Rate ◽  
Double Blind ◽  
Blocking Effects ◽  
The Mean ◽  
Exercise Induced ◽  
African Patients

1. The β-adrenoreceptor-blocking effects of pindolol were compared with those of propranolol and a placebo in a double-blind cross-over trial involving nine hypertensive African patients. 2. Heart rate, systolic blood pressure and diastolic blood pressure were measured at rest and immediately after exercise before and at intervals up to 6 h after oral administration of the drugs. In addition, plasma pindolol and propranolol concentrations were determined at the same intervals. 3. Pindolol diminished systolic blood pressure at rest and after exercise and antagonized exercise-induced tachycardia, but had no effect on resting heart rate. Propranolol diminished systolic blood pressure predominantly after exercise and reduced both resting and exercise heart rate. Both drugs had no effect on diastolic pressure. 4. The mean plasma concentration reached a peak at 2 h for each drug and this coincided with the interval at which maximal β-adrenoreceptor-blocking effect was observed.

scholarly journals Hypoxia preconditioning promotes endurance exercise capacity of mice by activating skeletal muscle Nrf2

2019 ◽  
Vol 127 (5) ◽  
pp. 1267-1277
Author(s):  
Linjia Wang ◽  
Simin Yang ◽  
Lu Yan ◽  
Hao Wei ◽  
Jianxiong Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Capacity ◽  
Treadmill Exercise ◽  
Related Factor ◽  
Nuclear Factor ◽  
Wild Type ◽  
Hypoxia Preconditioning ◽  
Nrf2 Knockout ◽  
Exercise Induced ◽  
Induced Changes

Elite endurance athletes are used to train under hypoxic/high-altitude conditions, which can elicit certain stress responses in skeletal muscle and helps to improve their physical performance. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates cellular redox homeostasis and metabolism in skeletal muscle, playing important roles in adaptation to various stresses. In this study, Nrf2 knockout (KO) and wild-type (WT) mice were preconditioned to 48 h of hypoxia exposure (11.2% oxygen), and the effects of hypoxia preconditioning (HP) on exercise capacity and exercise-induced changes of antioxidant status, energetic metabolism, and mitochondrial adaptation in skeletal muscle were evaluated. Nrf2 knockout (KO) and wild-type (WT) mice were exposed to normoxia or hypoxia for 48 h before taking incremental treadmill exercise to exhaustion under hypoxia. The skeletal muscles were collected immediately after the incremental treadmill exercise to evaluate the impacts of HP and Nrf2 on the exercise-induced changes. The results indicate the absence of Nrf2 did not affect exercise capacity, although the mRNA expression of certain muscular genes involved in antioxidant, glycogen and fatty acid catabolism was decreased in Nrf2 KO mice. However, 48-h HP enhanced exercise capacity in WT mice but not in Nrf2 KO mice, and the exercise capacity of WT mice was significantly higher than that of Nrf2 KO mice. These findings suggest HP promotes exercise capacity of mice with the participation of the Nrf2 signal in skeletal muscle. NEW & NOTEWORTHY Hypoxia preconditioning (HP) activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signal, which was involved in HP-elicited adaptation responses to hypoxia, oxidative, and metabolic stresses in skeletal muscle. On the other hand, Nrf2 deficiency abolished the enhanced exercise capacity after the 48-h HP. Our results indicate that Nrf2 plays an essential role in the exercise capacity-enhancing effect of HP, possibly by modulating muscular antioxidative responses, the mRNA expression of muscular genes involved in glycogen and fatty acid metabolism, as well as mitochondrial biogenesis, and through the cross talk with AMPK and hypoxia-inducible factor-1α signaling.

scholarly journals Cardiac hypertrophy and decreased high-density lipoprotein cholesterol in Lrig3-deficient mice

2016 ◽  
Vol 310 (11) ◽  
pp. R1045-R1052 ◽  
Author(s):  
Martin Hellström ◽  
Madelene Ericsson ◽  
Bengt Johansson ◽  
Mahmood Faraz ◽  
Fredrick Anderson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
High Density Lipoprotein ◽  
Heart Function ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Wild Type ◽  
Lipid Levels ◽  
Deficient Mice

Genetic factors confer risk for cardiovascular disease. Recently, large genome-wide population studies have shown associations between genomic loci close to LRIG3 and heart failure and plasma high-density lipoprotein (HDL) cholesterol level. Here, we ablated Lrig3 in mice and investigated the importance of Lrig3 for heart function and plasma lipid levels. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze Lrig3 expression in the hearts of wild-type and Lrig3-deficient mice. In addition, molecular, physiological, and functional parameters such as organ weights, heart rate, blood pressure, heart structure and function, gene expression in the heart, and plasma insulin, glucose, and lipid levels were evaluated. The Lrig3-deficient mice were smaller than the wild-type mice but otherwise appeared grossly normal. Lrig3 was expressed at detectable but relatively low levels in adult mouse hearts. At 9 mo of age, ad libitum-fed Lrig3-deficient mice had lower insulin levels than wild-type mice. At 12 mo of age, Lrig3-deficient mice exhibited increased blood pressure, and the Lrig3-deficient female mice displayed signs of cardiac hypertrophy as assessed by echocardiography, heart-to-body weight ratio, and expression of the cardiac hypertrophy marker gene Nppa. Additionally, Lrig3-deficient mice had reduced plasma HDL cholesterol and free glycerol. These findings in mice complement the human epidemiological results and suggest that Lrig3 may influence heart function and plasma lipid levels in mice and humans.

Repeated daily injections and osmotic pump infusion of isoproterenol cause similar increases in cardiac mass but have different effects on blood pressure

2005 ◽  
Vol 83 (2) ◽  
pp. 191-197 ◽  
Author(s):  
A Roger Hohimer ◽  
Lowell E Davis ◽  
Daniel C Hatton
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Body Weight ◽  
Cardiac Hypertrophy ◽  
Systemic Hemodynamic ◽  
Routes Of Administration ◽  
Arterial Blood ◽  
C57bl6 Mouse ◽  
Dose Dependent ◽  
Pump Infusion

We found in mice that repeated single daily subcutaneous (s.c.) isoproterenol (ISO) injections, like constant infusions using osmotic minipumps, caused increased biventricular mass or weight relative to body weight (VW/BW). We found that 5 (1/d) s.c. injections of 2, 10, or 20 µg/g body weight caused equivalent VW/BW increases as compared with 5-d infusions at 20 µg/(g·d)). While it is often presumed that ISO elicits hypertrophy by a direct effect on the myocytes, growth may also be secondary to systemic hemodynamic effects. The 2 modes of ISO administration had different effects on mean arterial blood pressure (MABP) and heart rate. Using telemetry we observed that single injections of ISO (0, 0.5, 2, and 10 µg/g) were associated with hypotension and tachycardia with a duration but not a magnitude that was dose dependent. MABP dropped rapidly to 60 mm Hg for more than 2 h at the highest dose. Constant s.c. infusion of ISO at 20 µg/(g·d) initially lowered MABP to about 70 mm Hg for 24 h. At 48 h MABP was normal, but rose 10 mm Hg higher than baseline by day 5. Thus, different routes of administration of ISO that cause comparable increases in VW/BW had different effects on MABP. Thus when evaluating mouse models of ISO-induced cardiac hypertrophy, both repeated daily injections or infusions can cause similar increases in VW/BW, but the daily doses that are required are not the same. Furthermore, these different routes of administration have different hemodynamic sequelae and could potentially evoke different cardiac phenotypes.Key words: C57BL6 mouse, hypotension, heart rate, cardiac hypertrophy, β-adrenergic.

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