Adrenergic responsiveness is reduced, while baseline cardiac function is preserved in old adult conscious monkeys

1995 ◽  
Vol 269 (5) ◽  
pp. H1664-H1671 ◽  
Author(s):  
N. Sato ◽  
K. Kiuchi ◽  
Y. T. Shen ◽  
S. F. Vatner ◽  
D. E. Vatner
Keyword(s):  
Adrenergic Receptor ◽  
Left Atrial ◽  
Pressure Gauge ◽  
Left Ventricular ◽  
Peripheral Vascular ◽  
Adrenergic Stimulation ◽  
First Derivative ◽  
Old Adult ◽  
Vascular Responsiveness ◽  
Isovolumic Relaxation

To examine the physiological deficit to adrenergic stimulation with aging, five younger adult (3 +/- 1 yr old) and nine older adult (17 +/- 1 yr old) healthy monkeys were studied after instrumentation with a left ventricular (LV) pressure gauge, aortic and left atrial catheters, and aortic flow probes to measure cardiac output directly. There were no significant changes in baseline hemodynamics in conscious older monkeys. For example, an index of contractility, the first derivative of LV pressure (LV dP/dt) was similar (3,191 +/- 240, young vs. 3,225 +/- 71 mmHg/s, old) as well as in isovolumic relaxation, tau (24.3 +/- 1.7 ms, young vs. 23.0 +/- 1.0 ms, old) was similar. However, inotropic, lusitropic, and chronotropic responses to isoproterenol (Iso; 0.1 micrograms/kg), norepinephrine (NE; 0.4 micrograms/kg), and forskolin (For; 75 nmol/kg) were significantly (P < 0.05) depressed in older monkeys. For example. Iso increased LV dP/dt by by 146 +/- 14% in younger monkeys and by only 70 +/- 5% in older monkeys. Iso also reduced tau more in younger monkeys (-28 +/- 7%) compared with older monkeys (-13 +/- 3%). Furthermore, peripheral vascular responsiveness to Iso, NE, For, and phenylephrine (PE; 5 micrograms/kg) was significantly (P < 0.05) reduced in older monkeys. For example, phenylephrine (5 micrograms/kg) increased total peripheral resistence by 69 +/- 4% in younger monkeys and by only 45 +/- 3% in older monkeys. Thus in older monkeys without associated cardiovascular disease, baseline hemodynamics are preserved, but adrenergic receptor responsiveness is reduced systemically, not just in the heart.

β-blockade abolishes the augmented cardiac tPA release induced by transactivation of heterodimerised bradykinin receptor-2 and β2-adrenergic receptor in vivo

2014 ◽  
Vol 112 (11) ◽  
pp. 951-959 ◽  
Author(s):  
Morten Eriksen ◽  
Arnfinn Ilebekk ◽  
Alessandro Cataliotti ◽  
Cathrine Rein Carlson ◽  
Torstein Lyberg ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Adrenergic Stimulation ◽  
Β2 Adrenergic Receptor ◽  
Β Blocker

SummaryBradykinin (BK) receptor-2 (B2R) and β2-adrenergic receptor (β2AR) have been shown to form heterodimers in vitro. However, in vivo proofs of the functional effects of B2R-β2AR heterodimerisation are missing. Both BK and adrenergic stimulation are known inducers of tPA release. Our goal was to demonstrate the existence of B2R-β2AR heterodimerisation in myocardium and to define its functional effect on cardiac release of tPA in vivo. We further investigated the effects of a non-selective β-blocker on this receptor interplay. To investigate functional effects of B2R-β2AR heterodimerisation (i. e. BK transactivation of β2AR) in vivo, we induced serial electrical stimulation of cardiac sympathetic nerves (SS) in normal pigs that underwent concomitant BK infusion. Both SS and BK alone induced increases in cardiac tPA release. Importantly, despite B2R desensitisation, simultaneous BK infusion and SS (BK+SS) was characterised by 2.3 ± 0.3-fold enhanced tPA release compared to SS alone. When β-blockade (propranolol) was introduced prior to BK+SS, tPA release was inhibited. A persistent B2R-β2AR heterodimer was confirmed in BK-stimulated and nonstimulated left ventricular myocardium by immunoprecipitation studies and under non-reducing gel conditions. All together, these results strongly suggest BK transactivation of β2AR leading to enhanced β2AR-mediated release of tPA. Importantly, non-selective β-blockade inhibits both SS-induced release of tPA and the functional effects of B2R-β2AR heterodimerisation in vivo, which may have important clinical implications.

Increased alpha 1-adrenergic vascular sensitivity during development of hypertension in conscious dogs

1993 ◽  
Vol 264 (4) ◽  
pp. H1259-H1268 ◽  
Author(s):  
N. Uemura ◽  
D. E. Vatner ◽  
Y. T. Shen ◽  
J. Wang ◽  
S. F. Vatner
Keyword(s):  
Adrenergic Receptor ◽  
Peripheral Resistance ◽  
Aortic Pressure ◽  
Conscious Dogs ◽  
Aortic Tissue ◽  
Ang Ii ◽  
Receptor Density ◽  
Adrenergic Stimulation ◽  
Before And After ◽  
Vascular Responsiveness

The goal of this study was to determine whether enhanced vascular responsiveness during the development of perinephritic hypertension is selective or nonspecific. The effects of graded infusions of norepinephrine (NE), phenylephrine (PE), angiotensin II (ANG II), and vasopressin (VP) were examined on mean arterial pressure, total peripheral resistance (TPR), and aortic pressure-diameter relationships in conscious dogs. NE increased TPR significantly greater (P < 0.01) in hypertension than normotension, as did PE infusion, whereas ANG II and VP increased TPR similarly before and after hypertension. Analysis of aortic pressure-diameter relationships also demonstrated significant (P < 0.05) shifts in response to NE and PE, but not ANG II and VP, during the development of hypertension. In normotensive dogs, low doses of ANG II infusion also enhanced the vasoconstrictor response not only to NE and PE but also to VP. In contrast to what was observed in hypertension, in the presence of ANG II infusion after ganglionic blockade, enhanced responses to PE and NE were no longer observed. The alpha 1-adrenergic receptor density in membrane preparations from aortic tissue, as determined by [3H]prazosin binding, was higher (P < 0.05) in hypertensive dogs than control dogs. Thus the vascular responsiveness in the aorta and resistance vessels is enhanced to alpha 1-adrenergic stimulation, but not to all vasoconstrictors, during developing perinephritic hypertension. The mechanism appears to involve increased alpha 1-adrenergic receptor density.

MRI assessment of LV relaxation by untwisting rate: a new isovolumic phase measure of τ

2001 ◽  
Vol 281 (5) ◽  
pp. H2002-H2009 ◽  
Author(s):  
Sheng-Jing Dong ◽  
Paul S. Hees ◽  
Cynthia O. Siu ◽  
James L. Weiss ◽  
Edward P. Shapiro
Keyword(s):  
Diastolic Function ◽  
Left Atrial ◽  
Independent Predictor ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Resonance Imaging ◽  
Relaxation Time Constant ◽  
Tagged Magnetic Resonance Imaging ◽  
Independent Assessment ◽  
Isovolumic Relaxation

Most noninvasive measures of diastolic function are made during left ventricular (LV) filling and are therefore subject to “pseudonormalization,” because variation in left atrial (LA) pressure may confound the estimation of relaxation rate. Counterclockwise twist of the LV develops during ejection, but untwisting occurs rapidly during isovolumic relaxation, before mitral opening. We hypothesized that the rate of untwisting might reflect the process of relaxation independent of LA pressure. Recoil rate (RR), the velocity of LV untwisting, was measured by tagged magnetic resonance imaging and regressed against the relaxation time constant (τ), recorded by catheterization, in 10 dogs at baseline and after dobutamine, saline, esmolol, and methoxamine treatment. RR correlated closely (average r = −0.86) with τ and was unaffected by elevated LA pressure. Multiple regression showed that τ, but not LA or aortic pressure, was an independent predictor of RR ( P < 0.0001, P = 0.99, and P = 0.18, respectively). The rate of recoil of torsion, determined wholly noninvasively, provides an isovolumic phase, preload-independent assessment of LV relaxation. Use of this novel parameter should allow the detailed study of diastolic function in states known to affect filling rates, such as aging, hypertension, and congestive heart failure.

scholarly journals The β3 Adrenergic Receptor Antagonist L-748,337 Attenuates Dobutamine-Induced Cardiac Inefficiency While Preserving Inotropy in Anesthetized Pigs

2021 ◽  
pp. 107424842110487
Author(s):  
Lars Rødland ◽  
Leif Rønning ◽  
Anders Benjamin Kildal ◽  
Ole-Jakob How
Keyword(s):  
Adrenergic Receptor ◽  
Myocardial Metabolism ◽  
Combined Treatment ◽  
Left Ventricular ◽  
Dobutamine Infusion ◽  
Cardiac Energetics ◽  
Adrenergic Stimulation ◽  
Cardiac Efficiency ◽  
Drug Infusion ◽  
Cardiac Inotropy

Excessive myocardial oxygen consumption (MVO2) is considered a limitation for catecholamines, termed oxygen cost of contractility. We hypothesize that increased MVO2 induced by dobutamine is not directly related to contractility but linked to intermediary myocardial metabolism. Furthermore, we hypothesize that selective β3 adrenergic receptor (β3AR) antagonism using L-748,337 prevents this. In an open-chest pig model, using general anesthesia, we assessed cardiac energetics, hemodynamics and arterial metabolic substrate levels at baseline, ½ hour and 6 hours after onset of drug infusion. Cardiac efficiency was assessed by relating MVO2 to left ventricular work (PVA; pressure–volume area). Three groups received dobutamine (5 μg/kg/min), dobutamine + L-748,337 (bolus 50 μg/kg), or saline for time-matched controls. Cardiac efficiency was impaired over time with dobutamine infusion, displayed by persistently increased unloaded MVO2 from ½ hour and 47% increase in the slope of the PVA–MVO2 relation after 6 hours. Contractility increased immediately with dobutamine infusion ( dP/ dt max; 1636 ± 478 vs 2888 ± 818 mmHg/s, P < 0.05) and persisted throughout the protocol (2864 ± 1055 mmHg/s, P < 0.05). Arterial free fatty acid increased gradually (0.22 ± 0.13 vs 0.39 ± 0.30 mM, P < 0.05) with peak levels after 6 hours (1.1 ± 0.4 mM, P < 0.05). By combining dobutamine with L-748,337 the progressive impairment in cardiac efficiency was attenuated. Interestingly, this combined treatment effect occurred despite similar alterations in cardiac inotropy and substrate supply. We conclude that the extent of cardiac inefficiency following adrenergic stimulation is dependent on the duration of drug infusion, and β3AR blockade may attenuate this effect.

Greater glycogen utilization during β1- than β2-adrenergic receptor stimulation in the isolated perfused rat heart

2007 ◽  
Vol 293 (6) ◽  
pp. E1828-E1835 ◽  
Author(s):  
Patrick McConville ◽  
Edward G. Lakatta ◽  
Richard G. Spencer
Keyword(s):  
Rat Heart ◽  
Adrenergic Receptor ◽  
Left Ventricular ◽  
Rate Pressure Product ◽  
Lv Function ◽  
Adrenergic Stimulation ◽  
Functional Responses ◽  
Perfused Rat Heart ◽  
Phosphorylation Potential ◽  
Isolated Perfused Rat Heart

Differences in energy metabolism during β1- and β2-adrenergic receptor (AR) stimulation have been shown to translate to differences in the elicited functional responses. It has been suggested that differential access to glycogen during β1- compared with β2-AR stimulation may influence the peak functional response and modulation of the response during sustained adrenergic stimulation. Interleaved 13C- and 31P-NMR spectroscopy was used during β1- and β2-AR stimulation at matched peak workload (2.5 times baseline) in the isolated perfused rat heart to monitor glycogen levels, phosphorylation potential, and intracellular pH. Simultaneous measurements of left ventricular (LV) function [LV developed pressure (LVDP)], heart rate (HR), and rate-pressure product (RPP = LVDP × HR) were also performed. The heart was perfused under both substrate-free (SF) conditions and with exogenous glucose (G). The greater glycogenolysis was observed during β1- than β2-AR stimulation with G (54% vs. 38% reduction, P = 0.006) and SF (92% vs. 79% reduction, P = 0.04) perfusions. The greater β1-AR-mediated glycogenolysis was correlated with greater ability to sustain the initial contractile response. However, with SF perfusion, the duration of this ability was limited: excessive early glycogen depletion caused an earlier decline in LVDP and phosphorylation potential during β1- than β2-AR stimulation. Therefore, endogenous glycogen stores are depleted earlier and to a greater extent, despite a slightly weaker overall inotropic response, during β1- than β2-AR stimulation. These findings are consistent with β1-AR-specific PKA-dependent glycogen phosphorylase kinase signaling.

Absence of right ventricular isovolumic relaxation in open-chest anesthetized dogs

1992 ◽  
Vol 263 (5) ◽  
pp. H1587-H1590 ◽  
Author(s):  
E. S. Myhre ◽  
B. K. Slinker ◽  
M. M. LeWinter
Keyword(s):  
Right Ventricular ◽  
Left Ventricular ◽  
Right Atrial ◽  
Relative Timing ◽  
Relaxation Period ◽  
First Derivative ◽  
Open Chest ◽  
Anesthetized Dogs ◽  
The Right ◽  
Isovolumic Relaxation

During the left ventricular (LV) pump cycle, peak negative first derivative of pressure vs. time (dP/dt) occurs very close to the end of LV ejection, and there is a well-defined isovolumic relaxation period. Despite similarities between the right ventricular (RV) and LV pump cycles, recent studies indicate uncertainty as to whether peak negative RV dP/dt occurs simultaneously with RV end ejection and whether there is an isovolumic relaxation period during the RV pump cycle. To study these questions, we recorded relative timing of peak negative RV dP/dt, RV end ejection, and right atrial-RV pressure crossover in the open-chest anesthetized dog. The data demonstrate that peak negative RV dP/dt occurs an average of 60 ms before end ejection and that there is no RV isovolumic relaxation period. These findings have implications for the possible use of peak negative RV dP/dt as a marker of RV end ejection and for how time constants of pressure decay obtained during RV relaxation can be interpreted.

Role of the papillary muscle in opening and closure of the mitral valve

1980 ◽  
Vol 238 (3) ◽  
pp. H348-H354 ◽  
Author(s):  
M. Marzilli ◽  
H. N. Sabbah ◽  
T. Lee ◽  
P. D. Stein
Keyword(s):  
Mitral Valve ◽  
Papillary Muscle ◽  
Left Atrial ◽  
Left Ventricular ◽  
Atrial Pressure ◽  
Left Atrial Pressure ◽  
Dimensional Changes ◽  
Opening And Closing ◽  
Isovolumic Relaxation

Dimensional changes of the left ventricular anterolateral papillary muscle of six open-chest dogs were measured continuously throughout the cardiac cycle in order to evaluate the role of the papillary muscle in opening and closing of the mitral valve. Dimensional changes were measured with ultrasonic dimension gauges. Maximal shortening and maximal elongation of the papillary muscle followed maximal shortening and elongation of a segment of the free wall of the left ventricle by 65 +/- 6 (SE) ms. Maximal elongation of the papillary muscle occurred 25 +/- 2 ms after the onset of ejection. Maximal shortening of the papillary muscle occurred 68 +/- 5 ms after the aortic incisura and 10 +/- 2 ms after the crossover of left ventricular and left atrial pressure. The papillary muscle shortened 14 +/- 4%. The percentage of papillary muscle shortening that occurred after the aortic incisura was 39 +/- 7%, and the percentage of shortening that occurred after the crossover of left ventricular and left atrial pressure was 3 +/- 1%. The observed shortening of the papillary muscle throughout left ventricular isovolumic relaxation suggests that the papillary muscle may have a role in opening the mitral valve. Conversely, elongation of the papillary muscle in the late portion of diastole appears necessary to permit proper closure of the mitral valve leaflets.

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