Impaired cardiovascular function in male rats with hypo- and hyperthyroidism: Involvement of imbalanced nitric oxide synthase levels

Author(s):  
Nasibeh Yousefzadeh ◽  
Sajad Jeddi ◽  
Asghar Ghasemi

Background and Objective: All three isoforms of nitric oxide (NO) synthase (NOS) are targets for thyroid hormones in cardiovascular system. The aim of this study was to assess effects of hypoand hyperthyroidism on inducible (iNOS), endothelial (eNOS), and neural (nNOS) NOS levels in aorta and heart tissues of male rats. Methods: Rats were divided into control, hypothyroid, and hyperthyroid groups; hypo- and hyperthyroidism were induced by adding propylthiouracil (500 mg/L) and L-thyroxine (12 mg/L) to drinking water for a period of 21 days, respectively. At day 21, systolic blood pressure, heart rate, left ventricular developed pressure (LVDP), peak rate of positive and negative (±dp/dt) changes in left ventricular pressure as well as NO metabolites (NOx) and iNOS, eNOS, and nNOS protein levels in aorta and heart were measured. Results: Compared to controls, LVDP and ±dp/dt were lower in both hypo- and hyperthyroid rats. Compared to controls, heart rate and systolic blood pressure were lower in hypothyroid and higher in hyperthyroid rats. NOx levels in the heart of hypothyroid rats were lower (53%) whereas in the heart and aorta of hyperthyroid rats were higher (56% and 40%) than controls. Compared to controls, hypothyroid rats had lower levels of eNOS, iNOS, and nNOS in aorta (16%, 34%, and 15%, respectively) and lower iNOS and higher nNOS in heart tissue (27% and 46%). In hyperthyroid rats, eNOS levels were lower (54% and 30%) and iNOS were higher (63%, and 35%) in the aorta and heart while nNOS was lower in the aorta (18%). Conclusion: Hypothyroidism increased while hyperthyroidism decreased ratio of eNOS/iNOS in aorta and heart; these changes of NOS levels were associated with impaired cardiovascular function.

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Heng-Jie Cheng ◽  
Tiankai Li ◽  
Che Ping Cheng

Background: Sildenafil (SIL), a selective inhibitor of PDE5 has been shown to exert profound beneficial effects in heart failure (HF). Recently we further found that SIL caused regression of cardiac dysfunction in a rat model with isoproterenol (ISO)-induced progressive HF. However, the molecular basis is unclear. We hypothesized that reversal of HF-induced detrimental alterations on the expressions of cardiac SR Ca 2+ -ATPase (SERCA2a), β-adrenergic receptors (AR) and nitric oxide synthase (NOS) isoforms by SIL may play a key role for its salutary role in HF. Methods: Left ventricular (LV) and myocyte function and the protein levels of myocyte β 1 - and β 3 - AR, SERCA2a, phospholamban (PLB) and three NOS were simultaneously evaluated in 3 groups of male rats (6/group): HF , 3 months (M) after receiving ISO (170 mg/kg sq for 2 days); HF/SIL , 2 M after receiving ISO, SIL (70 μg/kg/day sq via mini pump) was initiated and given for 1 M; and Controls (C). Results: Compared with controls, ISO-treated rats progressed to severe HF at 3 M after ISO followed by significantly decreased LV contractility (E ES , HF: 0.7 vs C: 1.2 mmHg/μl) and slowed LV relaxation, reductions in the peak velocity of myocyte shortening (77 vs 136 μm/sec), relengthening (62 vs 104 μm/sec) and [Ca 2+ ] iT (0.15 vs 0.24) accompanied by a diminished myocyte inotropic response to β-AR agonist, ISO (10 -8 M). These abnormalities were associated with concomitant significant decreases in myocyte protein levels of β 1 -AR (0.23 vs 0.64), SERCA2a (0.46 vs 0.80), PLB Ser16 /PLB ratio (0.24 vs 0.40) and eNOS (0.28 vs 0.46), but significantly increases in protein levels of β 3 -AR (0.29 vs 0.10) and iNOS (0.18 vs 0.08) with relatively unchanged nNOS. Chronic SIL prevented the HF-induced decreases in LV and myocyte contraction, relaxation, peak [Ca 2+ ] iT , and restored normal myocyte contractile response to ISO stimulation. With SIL, protein levels of myocyte β 1 - and β 3 -AR, SERCA2a were restored close to control values, but eNOS was significantly elevated than controls (0.77). Conclusions: Chronic SIL prevents HF-caused downregulation of cardiac β 1 -AR and reverse contrast changes between iNOS and β 3 -AR with SERCA 2a and eNOS expression, leading to the preservation of LV and myocyte function, [Ca 2+ ] iT , and β-adrenergic reserve.


2020 ◽  
pp. 147451512094458
Author(s):  
Zhongyou Li ◽  
Wentao Jiang ◽  
Yu Chen ◽  
Guanshi Wang ◽  
Fei Yan ◽  
...  

Objective: The role of sauna bathing in cardiovascular function treatment has been increasingly explored, but insufficient attention has been paid to its efficacy. We performed a meta-analysis to provide more evidence for the efficacy of sauna treatment in cardiovascular nursing. Methods: Sixteen peer-reviewed journal articles were screened to summarize the efficacy of the sauna on cardiovascular function. Both acute (0–30 min after the sauna) and short-term (2–4 weeks following the sauna treatment) efficacies were investigated. Results: For pooled acute efficacy, body temperature and heart rate significantly ( p<0.001) grew by 0.94℃ and 17.86 beats/min, respectively; reductions of 5.55 mmHg ( p<0.001) and 6.50 mmHg ( p<0.001) were also observed in systolic blood pressure and diastole blood pressure, respectively. For combined short-term efficacy, left ventricular ejection fraction (LVEF), 6-min walk distance, and flow-mediated dilation ( p<0.001) increased by 3.27%, 48.11 m, and 1.71%, respectively; greater amelioration in LVEF was observed in participants with lower LVEF. The proportion of patients with New York Heart Association class III and IV decreased by 10.9% and 12.2%, respectively. Systolic blood pressure, diastolic blood pressure, brain natriuretic peptide concentration, left ventricular end-diastolic dimension, cardiothoracic ratio, and left atrial dimension reduced by 5.26 mmHg ( p<0.001), 4.14 mmHg ( p<0.001), 116.66 pg/mL ( p<0.001), 2.79 mm ( p<0.001), 2.628% ( p<0.05), and 1.88 mm ( p<0.05), respectively, while the concentration of norepinephrine in the plasma remained unchanged. Conclusion: Sauna treatment was found to play a positive role in improving cardiovascular function and physical activity levels, especially in patients with low cardiovascular function. These findings reveal that thermal intervention may be a promising means for cardiovascular nursing.


2020 ◽  
Vol 6 (1) ◽  
pp. e000672 ◽  
Author(s):  
Karani Magutah ◽  
Kihumbu Thairu ◽  
Nilesh Patel

AimTo investigate effect of <10 min moderate intensity exercise on cardiovascular function and maximal oxygen consumption (V˙ O2max) among sedentary adults.MethodsWe studied 53 sedentary urbanites aged ≥50 years, randomised into: (1) male (MS) and (2) female (FS) undertaking three short-duration exercise (5–10 min) daily, and (3) male (ML) and (4) female (FL) exercising 30–60 min 3–5 days weekly. Resting systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate and V˙ O2max were measured at baseline and 8 weekly for 24 weeks.ResultsAt baseline, 50% MS, 61.5% ML, 53.8% FS and 53.8% FL had SBP ≥120 mm Hg, and 14.3% MS, 53.8% ML, 23.1% FS and 38.5% FL had DBP ≥80 mm Hg. At 24 weeks, where SBP remained ≥120 mm Hg, values decreased from 147±19.2 to 132.3±9.6 mm Hg (50% of MS), from 144±12.3 to 128±7.0 mm Hg (23.1% of ML), from 143.1±9.6 to 128.0±7.0 mm Hg (53.8% of FS) and from 152.3±23.7 to 129±3.7 mm Hg (30.8% of FL). For DBP ≥80 mm Hg, MS and FS percentages maintained, but values decreased from 101±15.6 to 84.5±0.7 mm Hg (MS) and 99.0±3.6 to 87.7±4.9 mm Hg (FS). In ML and FL, percentage with DBP ≥80 mm Hg dropped to 15.4% (86.1±6.5 to 82.5±3.5 mm Hg) and (91.4±5.3 to 83.5±0.71 mm Hg). V˙ O2max increased from 26.1±4.4 to 32.0±6.2 for MS, from 25.8±5.1 to 28.8±5.4 for ML (group differences p=0.02), from 20.2±1.8 to 22.7±2.0 for FS and from 21.2±1.9 to 24.2±2.7 for FL (groups differences p=0.38).ConclusionAccumulated moderate intensity exercise bouts of <10 min confer similar-to-better cardiovascular and V˙ O2max improvements compared with current recommendations among sedentary adults.


2017 ◽  
Vol 40 (2) ◽  
pp. 77-88 ◽  
Author(s):  
Kurt A. Spurgin ◽  
Anthony Kaprelian ◽  
Roberto Gutierrez ◽  
Vidyasagar Jha ◽  
Christopher G. Wilson ◽  
...  

1996 ◽  
Vol 91 (3) ◽  
pp. 275-281 ◽  
Author(s):  
Paolo Palatini ◽  
Pieralberto Visentin ◽  
Gianluigi Nicolosi ◽  
Vincenzo Mione ◽  
Paolo Stritoni ◽  
...  

1. To assess the clinical significance of supernormal left ventricular systolic function in the initial phase of hypertension, 635 never-treated 18–45-year-old borderline to mild hypertensive subjects (477 males, 158 females) were studied. All subjects underwent echocardiography, 24 h ambulatory blood pressure monitoring and 24 h urine collection for catecholamine dosage. 2. Subjects whose left ventricular shortening-stress relationship was above the 95% confidence intervals of 50 normotensive subjects of similar age and sex distribution were defined as having supernormal function. 3. Age, duration of hypertension and left ventricular mass were similar in the hypertensive subjects with normal (85%) and supernormal (15%) ejective performance. Subjects with supernormal function showed higher office systolic blood pressure (P < 0001), office heart rate (P = 0.03) and cardiac index (P < 0001). Conversely, 24 h systolic blood pressure, 24 h heart rate and 24 h catecholamine output did not differ according to left ventricular function. 4. In conclusion, the greater white-coat effect and the normal baseline sympathetic tone exhibited by the patients with increased performance suggest that supernormal left ventricular pump function is only a marker of the alerting reaction elicited by the echocardiographic examination.


2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Qian Fan ◽  
Zhaozhuo Niu ◽  
Liqing Ma

To explore the effect of trimetazidine (TMZ) in cardiomyopathy treatment. Literatures, related with TMZ treatment for cardiomyopathy, were retrieved between 1990 and February 2018 in the Pubmed, Embase, and Cochrane Library systems. Cardiopulmonary exercise testing [resting heart rate (RHR), peak heart rate (PHR), peak systolic blood pressure (PSBP), and resting systolic blood pressure (RSBP)] and echocardiographic results [left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), systolic wall thickening score index (SWTSI), left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD)] were merged to detect the publication bias. Total 898 patients with cardiomyopathy were divided into two groups: TMZ-treated group (n=456) and control group (n=442). There was no difference in the improvement of cardiomyopathy between the TMZ and control group. No publication bias was shown for PHR (t= 0.9791, P=0.5067). There were significant differences in LVEF, LVESV, SWTSI, LVESD, and LVEDD between the TMZ group and the control group. TMZ-treatment significantly increased the level of LVEF (95% confidence interval (CI): 5.46–7.84, P<0.001), and reduced the level of LVESV (95% CI: −18.73 to −7.77, P<0.001), SWTSI (95% CI: −0.47 to −0.15, Z = −3.85, P=0.001), LVESD (95% CI: −1.09 to −0.08, P<0.001), and LVEDD (95% CI: −0.55 to −0.26, P=0.023). There was no publication bias except for LVEDV (t = 2.5456, P=0.0438). TMZ is effective for cardiomyopathy treatment and worth to popularize in clinic.


1994 ◽  
Vol 86 (5) ◽  
pp. 523-529
Author(s):  
Hervé Perchet ◽  
Frédéric Pouillart ◽  
Anne Marie Duval-Moulin ◽  
Jean François Heintz ◽  
LUC Hittinger ◽  
...  

1. The physiological effects of the acute administration of a β-adrenoceptor antagonist in patients with idiopathic dilated cardiomyopathy were assessed by performing post-exercise Doppler-echocardiography study. Eleven patients and six control subjects were studied. According to a double-blind randomized protocol, 5 mg of metoprolol or placebo was administered before cycloergometer exercise. 2. In patients, after metopolol, a significant decrease in heart rate and systolic blood pressure, as well as in peak aortic acceleration and cardiac output, was observed 2 min after exercise. Left ventricular end-diastolic diameter did not change from baseline values either after placebo or metoprolol. In normal subjects, as compared with placebo, a decrease in heart rate and peak aortic acceleration was observed after metoprolol, whereas systolic blood pressure did not change. A similar increase in cardiac output occurred after metoprolol, as compared with placebo, associated with an increase in left ventricular end-diastolic diameter and stroke volume. 3. Post-exercise Doppler echocardiography is a means of assessing haemodynamic changes occurring during exercise in patients with congestive heart failure. Although acute metoprolol administration does not provide beneficial haemodynamic effects, a decrease in the energy requirements of the heart and a faster recovery after exercise may participate in the long-term beneficial action of β-adrenoceptor antagonists.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Takeuchi ◽  
M Nagai ◽  
K Dote ◽  
M Kato ◽  
N Oda ◽  
...  

Abstract Background Renal dysfunction is a frequent finding in patients hospitalized for acute heart failure (AHF). Worsening renal function (WRF) during hospitalization was found to be related with a poor outcome independently of baseline renal function. Early drop in systolic blood pressure (SBP) has shown to predict WRF in AHF. However, there have been few studies that reported the impact of on-admission heart rate (HR) on the relationship between early SBP drop and WRF in the elderly AHF. Purpose We assessed the hypothesis that early SBP drop predict WRF in the elderly patients with AHF, and investigated that on-admission HR might have an interaction with that relationship. Methods SBP and HR were measured on admission and 6 times during 48 hours in the 245 elderly AHF inpatients (82.9±6.0 years old, male 49.4%). WRF was defined as a serum creatinine increase of ≥0.3 mg/dL by Day 5. Early drop in SBP was calculated as the difference between admission and the lowest value measured during the first 48 hour of hospitalization. Results Early SBP drop (51.3 vs 32.5mmHg, p<0.01) and on-admission HR (79.3 vs 89.6bpm, p<0.05) were significantly different between the group with WRF (n=36) and the group without WRF (n=209). In the multiple logistic regression analysis adjusted for the confounders including age, gender, hypertension, left ventricular ejection fraction, total cholesterol, BNP, baseline creatinine, beta-blockade use, intravenous loop diuretic, isosorbide dinitrate and carperitide use, early SBP drop (OR: 1.003, 95% CI: 1.003–1.03, p<0.04) and on-admission HR (OR: 0.98, 95% CI: 0.96–0.99, p<0.01) were significantly associated with WRF. The interaction term of early SBP drop by on-admission HR did not have a significant association with WRF (p=0.3). Conclusions In the elderly AHF patients, exaggerated early SBP drop and lower on-admission HR were shown as significant independent predictors of WRF. These two factors were additively associated with WRF. Too much reduction in SBP and that in HR might be harmful to renal circulation in AHF.


1998 ◽  
Vol 85 (2) ◽  
pp. 758-763 ◽  
Author(s):  
Randall J. Lee ◽  
Richard E. Sievers ◽  
G. Joseph Gallinghouse ◽  
Philip C. Ursell

Atrioventricular (AV) block is a useful substrate for the study of cardiac physiology. The objective of this investigation was to develop a straightforward and reproducible model of permanent AV block in rats. Working through a sternotomy, we used an epicardial fat pad between the aortic root and the right atrial wall of the rat as a landmark for the site for injection of 70% ethanol (5–10 μl) into the myocardium 3 mm below the epicardial surface. Stable, complete heart block was produced in 23 of 28 rats (82%) with a success rate of 100% in the last 16 rats of the series. Saline injection produced no heart block in 15 rats. A separate group of 14 animals was allowed to recover. Chronic heart block was achieved in all ethanol-injected animals for up to 7 days before death. The survival rate in the recovered rats was 90% in the ethanol-injected group and 100% in the saline-injected control group. Acute hemodynamic changes following the production of heart block consisted of an increase in central venous pressure, a decrease in systolic blood pressure, a decrease in left ventricular pressure, and a decrease in change in pressure over time. Chronic hemodynamic changes demonstrated a return to baseline of the central venous pressure, a persistent decrease in systolic blood pressure, and a decrease in left ventricular pressure. After the rats were killed and the hearts were dissected, discrete areas of myocardial damage were identified histologically in the atrial septum near the AV conduction axis tissue in the ethanol-injected hearts. Complete heart block was associated only with lesions extending into the specialized muscle of the AV node or His bundle. Focal mild hemorrhage, inflammation, and damaged myocardial fibers were observed in the acute stage, whereas healing lesions were characterized by granulation tissue and fibrosis replacing conduction tissue. The simple technique described provides a reproducible model for permanent, complete heart block and the study of cardiac function.


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