Abstract 13438: The Role and Mechanism of Chronic Beta3-Adrenergic Receptor Blockade on the Progression of Heart Failure in a Rat Model

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Xiaoqiang Sun ◽  
Che Cheng ◽  
Jing Cao ◽  
Zhi Zhang ◽  
Tiankai Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Left Ventricular ◽  
Plasma Norepinephrine ◽  
Functional Responses ◽  
Generating Capacity ◽  
Precise Role ◽  
Mini Pump

Background: The negative inotrope and up-regulation of β 3 -adrenergic receptors (AR) in human and animal failing hearts suggest a direct and contributing role of cardiac β 3 -AR activation on the progression of congestive heart failure (CHF). However, its precise role is still being debated. We hypothesize that up-regulation of cardiac β 3 -AR is detrimental and chronic β 3 -AR blockade may prevent CHF-caused intrinsic defects of left ventricular (LV) myocyte force-generating capacity and relaxation and improve β-AR regulation, thereby limiting the progression of CHF. Methods: We compared the alterations of LV and myocyte functional responses and [Ca 2+ ] i transient ([Ca 2+ ] iT ) in SD rats divided into 3 groups (8/group): 1) CHF 3 months after isoproterenol (ISO) (170 mg/kg, sq, for 2 days); 2) ISO/β 3 -ANT , 2 months after receiving ISO, a selective β 3 -AR antagonist (ANT), L-748,337, was initiated (10 -7 M/kg/day, sq. by mini-pump) and was given for 1 month; and 3) Sham controls . Results: Compared with controls, the animals that received ISO treatment had CHF onset at 1 month and progressed to severe HF at 3 months after ISO. Plasma norepinephrine (NE) (1295 vs 259 pg/ml) increased 5-fold; whereas, stroke volume (SV) (39 vs 91 μl) and ejection fraction (EF) (39 vs 62%) significantly decreased, and LV end-diastolic pressure (P ED ) (13.9 vs 6.0 mmHg) was doubled. These changes were paralleled with about 50% reductions in cell contraction (dL/dt max , 93 vs 186 μm/s) and relaxation (dR/dt max , 96 vs 159 μm/s) associated with a significant decrease in the peak systolic [Ca 2+ ] iT , (0.17 vs 0.26). In addition, superfusion of ISO (10 -8 M) caused much less increases in dL/dt max (39 vs 68%), dR/dt max (23 vs 54%), and [Ca 2+ ] IT (14 vs 28%). Treatment with β 3 -ANT increased SV (89 μl) and EF (60%), decreased P ED more than 90% from ISO-treated values, and corrected the elevation of plasma NE (301 pg/ml), dL/dt max (184 μm/s), dR/dt max (152 μm/s), and [Ca 2+ ] iT (0.24). ISO-induced increase in dL/dt max and [Ca 2+ ] iT also returned close to control levels. Conclusion: Chronic β 3 -ANT treatment after CHF significantly improves LV and myocyte contractile function and [Ca 2+ ] i regulation and limits the development of CHF. Thus, β 3 -AR blocker may provide a new therapeutic strategy for the treatment of CHF.

Role of endogenous atrial natriuretic peptide on systemic and renal hemodynamics in heart failure rats

1994 ◽  
Vol 267 (1) ◽  
pp. H182-H186 ◽  
Author(s):  
T. Nishikimi ◽  
K. Miura ◽  
N. Minamino ◽  
K. Takeuchi ◽  
T. Takeda
Keyword(s):  
Heart Failure ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Diastolic Pressure ◽  
Urinary Sodium Excretion ◽  
Left Ventricular ◽  
Renal Hemodynamics ◽  
Renal Tubular ◽  
Atrial Natriuretic

To investigate the role of endogenous atrial natriuretic peptide (ANP) in rats with heart failure (HF), we administered HS-142-1 (HS; 3 mg/kg body wt iv), a novel nonpeptide ANP-receptor antagonist, to rats with surgically induced myocardial infarction and sham-operated rats. HF was characterized by a higher left ventricular end-diastolic pressure and higher plasma ANP concentration vs. controls. HS administration significantly reduced the plasma and urinary levels of guanosine 3',5'-cyclic monophosphate in rats with HF [plasma concentration 10.6 +/- 2.6 vs. 2.7 +/- 0.4 nM (P < 0.05); urinary excretion 48 +/- 8 vs. 12 +/- 2 pmol/min (P < 0.05)]. Systemic and renal hemodynamics were unaffected by HS administration. Urine flow (-35%) and urinary sodium excretion (-50%) were significantly decreased after HS only in those rats with HF that had no changes in systemic and renal hemodynamics. These results suggest that the elevated ANP levels in HF do not contribute directly to the maintenance of systemic hemodynamics but rather compensate for the HF mainly via diuresis and natriuresis, achieved by the inhibition of renal tubular reabsorption rather than by renal vasodilatation.

Factors involved in delaying the rise in peripheral resistance in developing heart failure

1994 ◽  
Vol 267 (1) ◽  
pp. H211-H216 ◽  
Author(s):  
K. Kiuchi ◽  
R. P. Shannon ◽  
N. Sato ◽  
M. Bigaud ◽  
C. Lajoie ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Peripheral Resistance ◽  
Left Ventricular ◽  
Right Atrial ◽  
Plasma Norepinephrine ◽  
Peripheral Vascular ◽  
Vascular Control ◽  
Developing Heart

The development of heart failure (HF) on peripheral vascular control was studied in 10 conscious dogs with measurements of cardiac output (CO) and left ventricular (LV), arterial, and right atrial pressures. At 3 wk after pacing-induced HF, CO was not decreased from 2.5 +/- 0.2 l/min, whereas LV dP/dt fell (from 2,858 +/- 71 to 1,409 +/- 69 mmHg/s) and LV end-diastolic pressure increased (from 4.8 +/- 0.4 to 27.3 +/- 1.1 mmHg) (P < 0.05). At 4–7 wk after pacing, CO was significantly decreased (to 1.6 +/- 0.1 l/min; P < 0.05), but total peripheral resistance (TPR) did not rise, despite increases in plasma norepinephrine and renin activity (P < 0.05). In the presence of ganglionic blockade, TPR was still not increased in HF. In vitro studies in isolated femoral artery segments demonstrated reduced intrinsic tone (0.028 +/- 0.007 g/mg; P < 0.05) as compared with vessels from sham-operated controls (0.124 +/- 0.023 g/mg), whereas the intracellular calcium level was not altered in HF. Thus, during the development of HF, severe contractile dysfunction precedes the fall in CO, which, in turn, precedes the rise in TPR. The delayed rise in TPR appears to involve a reduction in intrinsic peripheral vascular tone, despite neurohumoral activation.

Progressive myocardial dysfunction associated with increased vascular resistance

1980 ◽  
Vol 239 (4) ◽  
pp. H477-H477 ◽  
Author(s):  
Joseph A. Franciosa ◽  
Richard Heckel ◽  
Catherine Limas ◽  
Jay N. Cohn
Keyword(s):  
Heart Failure ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Diastolic Pressure ◽  
Myocardial Dysfunction ◽  
Peripheral Circulation ◽  
Left Ventricular ◽  
Stroke Work ◽  
Low Cardiac Output

To study heart failure from a myocardial lesion, we injected glass beads into the circumflex coronary artery of 11 conscious dogs and followed hemodynamics for 10 mo. Heart rate remained unchanged. Control mean arterial pressure of 112.3 ± 3.0 (SE) mmHg was unchanged at 1 and 3 mo, but rose to 127.2 ± 8.5 to 84.0 ± 7.6 ml . kg-1 . min-1 at 10 mo (P < 0.02), but was unchanged at 1 and 3 mo. Left ventricular end-diastolic pressure (LVEDP) averaged 4.6 ± 0.8 mmHg at control and rose to 11.8 ± 1.4 mmHg at 1 mo and 14.9 ± 2.5 mmHg at 10 mo (both P < 0.01). Systemic vascular resistance rose significantly by 10 mo. The ratio of stroke work to LVEDP fell from 13.1 ± 0.1 at control to 3.8 ± 0.5 by 10 mo (P < 0.01). In this dog model, left ventricular dysfunction is manifest early by increased LVEDP and later by high systemic vascular resistance with low cardiac output, thus suggesting a role of the peripheral circulation in the progression of heart failure.

Redistribution and abnormal activity of phospholipase A2 isoenzymes in postinfarct congestive heart failure

2001 ◽  
Vol 280 (3) ◽  
pp. C573-C580 ◽  
Author(s):  
Jane McHowat ◽  
Paramjit S. Tappia ◽  
Song-Yan Liu ◽  
Raetreal McCrory ◽  
Vincenzo Panagia
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Phospholipase D ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Immunoblot Analysis ◽  
Left Ventricular ◽  
Hemodynamic Assessment ◽  
Intracellular Ca ◽  
Contractile Performance

Cardiac sarcolemmal (SL) cis-unsaturated fatty acid sensitive phospholipase D ( cis-UFA PLD) is modulated by SL Ca2+-independent phospholipase A2(iPLA2) activity via intramembrane release of cis-UFA. As PLD-derived phosphatidic acid influences intracellular Ca2+ concentration and contractile performance of the cardiomyocyte, changes in iPLA2 activity may contribute to abnormal function of the failing heart. We examined PLA2 immunoprotein expression and activity in the SL and cytosol from noninfarcted left ventricular (LV) tissue of rats in an overt stage of congestive heart failure (CHF). Hemodynamic assessment of CHF animals showed an increase of the LV end-diastolic pressure with loss of contractile function. In normal hearts, immunoblot analysis revealed the presence of cytosolic PLA2 (cPLA2) and secretory PLA2 (sPLA2) in the cytosol, with cPLA2 and iPLA2 in the SL. Intracellular PLA2 activity was predominantly Ca2+independent, with minimal sPLA2 activity. CHF increased cPLA2 immunoprotein and PLA2 activity in the cytosol and decreased SL iPLA2 and cPLA2immunoprotein and SL PLA2 activity. sPLA2activity and abundance decreased in the cytosol and increased in SL in CHF. The results show that intrinsic to the pathophysiology of post-myocardial infarction CHF are abnormalities of SL PLA2isoenzymes, suggesting that PLA2-mediated bioprocesses are altered in CHF.

scholarly journals Changes of renal AQP2, ENaC, and NHE3 in experimentally induced heart failure: response to angiotensin II AT1 receptor blockade

2009 ◽  
Vol 297 (6) ◽  
pp. F1678-F1688 ◽  
Author(s):  
Sophie C. Lütken ◽  
Soo Wan Kim ◽  
Thomas Jonassen ◽  
David Marples ◽  
Mark A. Knepper ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Diastolic Pressure ◽  
Collecting Duct ◽  
Left Ventricular ◽  
Outer Medulla ◽  
Outer Stripe ◽  
Medullary Collecting Duct ◽  
Type 3

Heart failure (HF) was induced by ligation of the left anterior descending artery (LAD). Left ventricular end-diastolic pressure (LVEDP) >25 mmHg (at day 23 after LAD ligation) was the inclusion criterion. The rats were divided into three groups: sham-operated (Sham, n = 23, LVEDP: 5.6 ± 0.6 mmHg), HF ( n = 14, LVEDP: 29.4 ± 1.4 mmHg), and candesartan (1 mg·kg−1·day−1 sc)-treated HF (HF + Can, n = 9, LVEDP: 29.2 ± 1.2 mmHg). After 7 days (i.e., 29 days after LAD ligation) semiquantitative immunoblotting revealed increased abundance of inner medulla aquaporin-2 (AQP2) and AQP2 phosphorylated at Ser256 (p-AQP2) in HF. There was also markedly enhanced apical targeting of AQP2 and p-AQP2 in inner medullary collecting duct (IMCD) in HF compared with Sham rats, shown by immunocytochemistry. Candesartan treatment significantly reversed the increases in both AQP2 and p-AQP2 expression and targeting. In contrast, there were only modest changes in other collecting duct segments. Semiquantitative immunoblots revealed increased expression of type 3 Na+/H+ exchanger (NHE3) and Na+-K+-2Cl− cotransporter (NKCC2) in kidneys from HF compared with Sham rats: both effects were reversed or prevented by candesartan treatment. The protein abundance of α-epithelial sodium channel (α-ENaC) was increased while β-ENaC and γ-ENaC expression was decreased in the cortex and outer stripe of the outer medulla in HF compared with Sham rats, which was partially reversed by candesartan treatment. These findings strongly support an important role of angiotensin II in the pathophysiology of renal water and sodium retention associated with HF.

scholarly journals A Novel Small Molecule Troponin Activator Increases Cardiac Contractile Function Without Negative Impact on Energetics

2021 ◽  
Author(s):  
Huamei He ◽  
Tomas Baka ◽  
James Balschi ◽  
Alykhan S. Motani ◽  
Kathy K. Nguyen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Negative Impact ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Left Ventricular ◽  
Rate Pressure Product ◽  
Intact Mouse ◽  
Term Survival ◽  
Rat Hearts

Background: Current heart failure (HF) therapies unload the failing heart without targeting the underlying problem of reduced cardiac contractility. Traditional inotropes (i.e. calcitropes) stimulate contractility via energetically costly augmentation of calcium cycling and worsen patient survival. A new class of agents - myotropes - activate the sarcomere directly, independent of calcium. We hypothesize that a novel myotrope TA1 increases contractility without the deleterious myocardial energetic impact of a calcitrope dobutamine. Methods: We determined the effect of TA1 in bovine cardiac myofibrils and human cardiac microtissues, ex vivo in mouse cardiac fibers and in vivo in anesthetized normal rats. Effects of increasing concentrations of TA1 or dobutamine on contractile function, phosphocreatine (PCr) and ATP concentrations and ATP production were assessed by 31 P NMR spectroscopy on isolated perfused rat hearts. Results: TA1 increased the rate of myosin ATPase activity in isolated bovine myofibrils and calcium sensitivity in intact mouse papillary fibers. Contractility increased dose dependently in human cardiac microtissues and in vivo in rats as assessed by echocardiography. In isolated rat hearts, TA1 and dobutamine similarly increased rate pressure product (RPP). Dobutamine increased both developed pressure (DevP) and heart rate (HR) accompanied by decreased PCr to ATP ratio and decreased free energy of ATP hydrolysis (ΔG~ ATP ) and elevated left ventricular end-diastolic pressure (LVEDP). In contrast, the TA1 increased DevP without any effect on HR, LVEDP, PCr/ATP ratio or ΔG~ ATP . Conclusions: Novel myotrope, TA1, increased myocardial contractility by sensitizing the sarcomere to calcium without impairing diastolic function or depleting the cardiac energy reserve. Since energetic depletion negatively correlates with long term survival, myotropes may represent a superior alternative to traditional inotropes in heart failure management.

Abstract 035: Mechanism of Chronic CaMKII Inhibition-Caused Regression of Heart Failure: Beneficial Effects on Neurohormonal Activation, Left Ventricular and Cardiomyocyte Contractile Function, [Ca 2 +]i Regulation and Beta-Adrenergic Modulation

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Che Ping Cheng ◽  
Qun Shao ◽  
Heng-Jie Cheng ◽  
Michael F Callahan
Keyword(s):  
Heart Failure ◽  
Contractile Function ◽  
Left Ventricular ◽  
Functional Responses ◽  
Beneficial Effects ◽  
Adrenergic Modulation ◽  
Dependent Protein ◽  
System Activation ◽  
Contraction And Relaxation ◽  
To Receive

Background: Recent evidence indicates that Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) is upregulated in heart failure (HF), contributing to electric, structural and functional remodeling. CaMKII has been proposed to be a therapeutic target for HF. However, the role and mechanism of chronic CaMKII inhibition (I) in HF is unclear. We assessed the hypothesis that CaMKII I improves cardiomyocyte function, [Ca 2+ ] i regulation, and β-adrenergic reserve, thus limiting HF progression. Methods: We compared left ventricular (LV) and myocyte functional responses and plasma levels of norepinephrine (NE) over a period of 16 weeks (W) in 6 control (C) and 14 rats with HF induced by isoproterenol (ISO) (170 mg/kg sq for 2 days). After ISO for 12 weeks, HF animals were assigned to receive 4 W treatment with: placebo (saline) (n=6), KN-93 (70 µg/kg/day sq via mini pump) (n=6), or KN-92 (70 µg/kg/day sq via pump) (n=2), respectively. Results: Compared with C, ISO-treated rats had HF onset at 4 W after ISO and progressed to severe HF at 16 W with increased plasma NE (1398 vs 342 pg/ml), decreased ejection fraction (EF, 37% vs 62%) and LV contractility (E ES , 0.8 vs 1.3 mmHg/μl). LV time constant of relaxation (τ) (17.8 vs 10.6 ms) increased, accompanied with significant reductions in cell contraction (dL/dt max , 78 vs 151 μm/s), relaxation (dR/dt max , 59 vs 114 μm/s) and [Ca 2+ ] i transient ([Ca 2+ ] iT ) (0.18 vs 0.28). HF myocyte response to β-AR stimulation (ISO, 10 -8 M) was attenuated with significantly less increases in dL/dt max (34% vs 79%) and [Ca 2+ ] iT (19% vs 36%). The LV and myocyte dysfunction persisted in KN-92-treated HF group. In contrast, treatment with KN-93 significantly increased E ES (1.2 mmHg/μl) and EF (60%), decreased τ (12.1 ms) and corrected the elevation of plasma NE (319 pg/ml). Importantly, basal myocyte contraction (dL/dt max ,147 μm/s), relaxation (dR/dt max ,107 μm/s), and [Ca 2+ ] iT (0.25) improved. ISO-induced increase in dL/dt max (71%) and [Ca 2+ ] iT (32%) were augmented and close to normal control levels. Conclusion: Chronic CaMKII I prevents HF-induced sympathetic nervous system activation and improves LV and cardiomyocyte basal and β-AR stimulated contraction and relaxation, thus playing a salutary role at later stages of HF.

Hemodynamic and norepinephrine responses to pacing-induced heart failure in conscious sinoaortic-denervated dogs

1996 ◽  
Vol 81 (4) ◽  
pp. 1855-1855 ◽  
Author(s):  
Marian Brändle ◽  
Kaushik P. Patel ◽  
Wei Wang ◽  
Irving H. Zucker
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Control Level ◽  
Left Ventricular ◽  
Plasma Norepinephrine ◽  
Hemodynamic Parameters ◽  
Ventricular Pacing ◽  
Arterial Baroreflex ◽  
Failure State ◽  
Observation Period

Brändle, Marian, Kaushik P. Patel, Wei Wang, and Irving H. Zucker. Hemodynamic and norepinephrine responses to pacing-induced heart failure in conscious sinoaortic-denervated dogs. J. Appl. Physiol. 81(4): 1855–1862, 1996.—The present study was undertaken to determine the effects of chronic sinoaortic (baroreceptor) denervation (SAD) on the hemodynamic and sympathetic alterations that occur in the pacing-induced model of congestive heart failure. Two groups of dogs were examined: intact ( n = 9) and SAD ( n = 9). Both groups of dogs were studied in the control (prepace) state and each week after the initiation of ventricular pacing at 250 beats/min. After the pacemaker was turned off, hemodynamic and plasma norepinephrine levels returned toward control levels in the prepaced state and after 1 and 2 wk of pacing. However, by 3 wk all hemodynamic and norepinephrine levels remained relatively constant over the 10-min observation period with the pacemaker off. With the pacemaker off, left ventricular end-diastolic pressure went from 2.7 ± 1.4 (SE) mmHg during the prepace state to 23.2 ± 2.9 mmHg in the heart failure state in intact dogs ( P < 0.01). Left ventricular end-diastolic pressure increased to 27.1 ± 2.2 mmHg from a control level of 4.2 ± 1.9 mmHg in SAD dogs ( P < 0.0003). Mean arterial pressure significantly decreased in intact and SAD dogs. Resting heart rate was significantly higher in SAD dogs and increased to 135.8 ± 8.9 beats/min in intact dogs and 136.1 ± 6.5 beats/min in SAD dogs. There were no significant differences in the hemodynamic parameters between intact and SAD dogs after pacing. Plasma norepinephrine was significantly lower in intact than in SAD dogs before pacing (197.7 ± 21.6 vs. 320.6 ± 26.6 pg/ml; P < 0.005). In the heart failure state, plasma norepinephrine increased significantly in both intact (598.3 ± 44.2 pg/ml) and SAD (644.0 ± 64.6 pg/ml) groups. There were no differences in the severity or the magnitude of the developed heart failure state in SAD vs. intact dogs. We conclude from these data that the arterial baroreflex is not the sole mechanism for the increase in sympathetic drive in heart failure.

Abstract 69: Cardiomyocyte GSK-3α Signaling Exacerbate Pressure Overload-induced Dilated Cardiomyopathy and Heart Failure

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Firdos Ahmad ◽  
Hind Lal ◽  
Vipin K Verma ◽  
Qinkun Zhang ◽  
James R Woodgett ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Glycogen Synthase ◽  
Contractile Function ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Tamoxifen Treatment ◽  
Control Group ◽  
Lv Remodeling

Chronic pressure-overload (PO) induced-dilated cardiomyopathy (DCM) is one of the leading causes of left ventricular (LV) remodeling and heart failure. The role of glycogen synthase kinase-3α (GSK-3α) in PO-induced remodeling is not clear and existing dataset with global transgenic and knockout (KO) models show opposing roles. We sought to identify the specific role of GSK-3α in PO-induced dilatative cardiac remodeling. To better understand the role of GSK-3α, we employed cardiomyocyte-specific GSK3A ( GSK3A fl/fl MerCreMer ) KO mice. Post-tamoxifen treatment, the GSK-3α KO and littermate control mice underwent sham or trans-aortic constriction (TAC) surgery. Heart function was assessed at 0, 2, 4 and 6 week post-TAC using serial M-mode echocardiography. Cardiac function in the KOs and littermate controls declines equally up to 2 weeks of TAC. At 4 week, KO hearts underwent further hypertrophy, retaining concentric LV remodeling and preserved contractile function both at systole and diastole. In contrast, wild-type LV showed significant chamber dilatation with an impaired contractility. Significantly reduced LV chamber dilatation [LVIDd(mm); 5.4±0.4 vs. 4.9±0.4, P =0.01] and preserved contractile function [LVEF(%); 22.2±12.6 vs. 40.0±18.7, P =0.02] remains same in the KO mice until the end of the study (6 wk). Furthermore, LV posterior wall thickness in the KO hearts, both at systole and diastole, were significantly greater in comparison to the controls. Consistent with preserved LV dimension, significantly less mortality was observed in the KO vs. control group during the remodeling phase. Histological analysis of heart sections further revealed better preserved LV chamber and protection against TAC-induced cellular hypertrophy in the GSK-3α KOs. Moreover, KO hearts showed significantly less fibrosis accompanied with low level of cardiomyocyte apoptosis post-6 wk of TAC. Taken together, these observations show that cardiomyocyte-specific deletion of GSK-3α protects against chronic PO-induced adverse LV remodeling and preserves contractile function. Inhibiting specifically GSK-3α using isoform-specific inhibitor could be a viable therapeutic strategy to limit the PO-induced DCM, adverse remodeling and heart failure.

scholarly journals Estrogen restores role of basal nitric oxide in control of vascular tone in rats with chronic heart failure

1998 ◽  
Vol 274 (6) ◽  
pp. H2094-H2099 ◽  
Author(s):  
Ali Akbar Nekooeian ◽  
Catherine C. Y. Pang
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Diastolic Pressure ◽  
Peripheral Resistance ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Ovariectomized Rats ◽  
17Β Estradiol

This study examined the cardiovascular effects of 17β-estradiol in ovariectomized rats with heart failure. Two groups (50–60 days old) were implanted with 60-day-release pellets containing 17β-estradiol (25 μg/day) or vehicle at 7 days before ligation of the left coronary artery. Another group was sham operated and given vehicle pellets. After 7 wk, they were studied under pentobarbital anesthesia. Relative to sham-operated rats, ligated rats had reduced mean arterial pressure (MAP, −24 ± 6 mmHg), cardiac output (−27 ± 4 ml/min), left ventricular (LV) end-systolic pressure (−29 ± 8 mmHg), depressor responses to ACh (−6 ± 4 mmHg at 7.2 μg/kg) and sodium nitroprusside (SNP, −22 ± 6 mmHg at 9 μg/kg), and pressor responses to N G-nitro-l-arginine methyl ester (l-NAME, −14 ± 6 mmHg at 8 mg/kg) and increased LV end-diastolic pressure (LVEDP, 10.3 ± 0.8 mmHg) but no change in total peripheral resistance (TPR). Treatment of ligated rats with 17β-estradiol reduced TPR (−0.19 ± 0.06 mmHg ⋅ min ⋅ ml−1), LVEDP (−3.6 ± 1 mmHg), and responses to ACh (−16 ± 4 mmHg) and augmented responses tol-NAME (14 ± 3 mmHg) but did not alter other variables. Therefore, 17β-estradiol reduces preload and afterload and restores the vasodilator role of basal nitric oxide in ovariectomized rats with chronic heart failure.

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