Species differences in regulation of alpha-adrenergic receptor function

1989 ◽  
Vol 257 (5) ◽  
pp. R1110-R1116 ◽  
Author(s):  
Y. T. Shen ◽  
D. E. Vatner ◽  
H. E. Gagnon ◽  
S. F. Vatner
Keyword(s):  
Adrenergic Receptor ◽  
Maximum Rate ◽  
Species Differences ◽  
Mammalian Species ◽  
Left Ventricular ◽  
Receptor Density ◽  
Adrenergic Agonists ◽  
Receptor Stimulation ◽  
Alpha Adrenergic Receptor ◽  
Pressure Development

The effects of alpha-adrenergic receptor stimulation with norepinephrine and phenylephrine after beta-adrenergic and muscarinic receptor blockades were compared in conscious baboons, calves, dogs, and rats in which left ventricular (LV) pressure. LV maximum rate of pressure development (dP/dt), and heart rate were measured. Autonomic receptor density was examined in crude sarcolemmal preparations from the hearts. The major physiological differences were observed in rats, where alpha 1-adrenergic receptor stimulation resulted in the greatest (P less than 0.05) increases in LV dP/dt (29 +/- 2%) in response to phenylephrine, 5.0 micrograms/kg, in comparison with responses in dogs (12 +/- 4%), calves (3 +/- 3%), and baboons (1 +/- 2%). This was associated with the greatest (P less than 0.05) alpha 1-adrenergic receptor density in the rat heart (73 +/- 5 fmol/mg) compared with values in the baboon (6 +/- 1 fmol/mg), calf (21 +/- 3 fmol/mg), or dog (10 +/- 3 fmol/mg) myocardium. Thus there are major differences among mammalian species in alpha-adrenergic receptor density and physiological responsiveness to alpha-adrenergic agonists.

scholarly journals Adenylyl cyclase type 5 protein expression during cardiac development and stress

2009 ◽  
Vol 297 (5) ◽  
pp. H1776-H1782 ◽  
Author(s):  
Che-Lin Hu ◽  
Rachna Chandra ◽  
Hui Ge ◽  
Jayashree Pain ◽  
Lin Yan ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Adrenergic Receptor ◽  
Ventricular Hypertrophy ◽  
Cardiac Development ◽  
Mammalian Species ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Receptor Stimulation ◽  
Specific Antibodies ◽  
The Brain

Adenylyl cyclase (AC) types 5 and 6 (AC5 and AC6) are the two major AC isoforms expressed in the mammalian heart that mediate signals from β-adrenergic receptor stimulation. Because of the unavailability of isoform-specific antibodies, it is difficult to ascertain the expression levels of AC5 protein in the heart. Here we demonstrated the successful generation of an AC5 isoform-specific mouse monoclonal antibody and studied the expression of AC5 protein during cardiac development in different mammalian species. The specificity of the antibody was confirmed using heart and brain tissues from AC5 knockout mice and from transgenic mice overexpressing AC5. In mice, the AC5 protein was highest in the brain but was also detectable in all organs studied, including the heart, brain, lung, liver, stomach, kidney, skeletal muscle, and vascular tissues. Western blot analysis showed that AC5 was most abundant in the neonatal heart and declined to basal levels in the adult heart. AC5 protein increased in the heart with pressure-overload left ventricular hypertrophy. Thus this new AC5 antibody demonstrated that this AC isoform behaves similarly to fetal type genes, such as atrial natriuretic peptide; i.e., it declines with development and increases with pressure-overload hypertrophy.

Left ventricular function and beta-adrenoceptors in rabbit failing heart

1990 ◽  
Vol 258 (3) ◽  
pp. H634-H641 ◽  
Author(s):  
N. Gilson ◽  
N. el Houda Bouanani ◽  
A. Corsin ◽  
B. Crozatier
Keyword(s):  
Adrenergic Receptor ◽  
Volume Overload ◽  
Conscious State ◽  
Left Ventricular ◽  
Lv Function ◽  
Receptor Density ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Beta Adrenoceptors ◽  
Chronotropic Response

Few models of heart failure (HF) are available for physiological and pharmacological studies. We report here a model of pressure plus volume overload induced in rabbits in which left ventricular (LV) function was studied in the conscious state after instrumentation of the animals with LV pressure catheter and ultrasonic crystals measuring LV diameter. Beta-Adrenoceptors were studied on crude membranes obtained from control (C) and HF rabbits using [3H]CGP 12177. LV weights and end-diastolic diameters were significantly increased in the HF group compared with the C group (by 79 and 38%, respectively). The percentage of diameter systolic shortening was decreased, in the control state, in rabbits with HF (15.3 +/- 1.6%) as compared with C rabbits (29.6 +/- 2.5%) and remained lower in the HF group when end-systolic pressures were matched. Chronotropic response to isoproterenol injection was significantly decreased in rabbits with HF compared with that of C rabbits. Beta-Adrenergic receptor density was decreased in rabbits with HF (39.3 +/- 3.7 fmol/mg) compared with C rabbits (56.7 +/- 4.2 fmol/mg) without affinity changes. This model of chronic HF thus produces a marked hypertrophy with ventricular dilatation and a depression of LV function within 2 mo, factors that are associated with a reduced cardiac responsiveness to catecholamines and a decreased ventricular beta-adrenergic receptor density.

Mechanisms of denervation supersensitivity in regionally denervated canine hearts

1993 ◽  
Vol 264 (3) ◽  
pp. H815-H820 ◽  
Author(s):  
M. R. Warner ◽  
P. L. Wisler ◽  
T. D. Hodges ◽  
A. M. Watanabe ◽  
D. P. Zipes
Keyword(s):  
Adrenergic Receptor ◽  
Left Ventricular ◽  
Receptor Density ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Functional Studies ◽  
Denervation Supersensitivity ◽  
Stimulatory G Protein ◽  
Biochemical Analyses ◽  
Gs Alpha

Mechanisms responsible for “denervation supersensitivity” in regionally denervated canine hearts were examined by measuring beta-adrenergic receptor density and affinity and the density of the alpha-subunit of the stimulatory G protein (Gs alpha). Sympathetic denervation was produced by applying an epicardial strip of phenol midway between the left ventricular (LV) base and apex. Six to eight days after denervation, dogs were anesthetized and then underwent functional studies (n = 4) or hearts were excised for biochemical analyses (n = 6). Biochemical studies were also done on 3 nondenervated hearts. Effective refractory periods (ERPs) were measured in innervated (base) and denervated (apex) LV myocardium. During sympathetic stimulation (2 and 4 Hz), the ERP shortened more (P < 0.05) at basal than at apical sites, whereas during norepinephrine infusion (0.05 to 0.5 mg.kg-1 x min-1), the ERP shortened more (P < 0.001) at apical than at basal sites. In regionally denervated hearts, however, the density and affinity of beta-adrenergic receptors did not differ significantly (P > 0.2) in nondenervated basal compared with denervated apical myocardium. Quantitative immunoblotting of the Gs alpha demonstrated that the density of the 47- and 52-kDa subunits was also similar (P > 0.6) in basal compared with apical myocardium from regionally denervated hearts. In addition, beta-adrenergic receptor density and affinity and Gs alpha density did not differ significantly (P > 0.5) in basal compared with apical myocardium from nondenervated control hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of age and hypoxia on beta-adrenergic receptors in rat heart

1991 ◽  
Vol 71 (6) ◽  
pp. 2094-2098 ◽  
Author(s):  
S. L. Mader ◽  
C. L. Downing ◽  
E. Van Lunteren
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Left Ventricular ◽  
Hypoxic Exposure ◽  
Receptor Density ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Young Rats ◽  
Age Related

Previous reports suggest that hypoxia downregulates cardiac beta-adrenergic receptors from young rats. Because aging alters response to stress, we hypothesized an age-related alteration in the response to hypoxia. Male Fischer-344 rats, aged 3 and 20 mo, were divided into control and hypoxic groups. The hypoxic rats were exposed to hypobaric hypoxia (0.5 atm) for 3 wk. After hypoxic exposure, body weight decreased, hematocrit increased, right ventricular weight increased, and left ventricular weight decreased in all animals. beta-Adrenergic receptor density declined after hypoxic exposure in the young but not in the older animals, a change that was confined to the left ventricle. beta-Adrenergic receptor density in the right ventricle was significantly lower in the older animals than in the young animals. Plasma catecholamines (norepinephrine, epinephrine) drawn after the animals were killed (stress levels) decreased in young rats and increased in old rats after the exposure to hypoxia. Hypoxia is a useful physiological stress that elucidates age-related changes in cardiac beta-adrenergic receptor and catecholamine regulation that have not previously been described.

Force-frequency effect is a powerful determinant of myocardial contractility in the mouse

1997 ◽  
Vol 273 (3) ◽  
pp. H1283-H1290 ◽  
Author(s):  
V. Palakodeti ◽  
S. Oh ◽  
B. H. Oh ◽  
L. Mao ◽  
M. Hongo ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Myocardial Contractility ◽  
Sinus Node ◽  
Left Ventricular ◽  
Atrial Pacing ◽  
Force Frequency ◽  
Beta Adrenergic Receptor ◽  
Receptor Stimulation ◽  
Beta Adrenergic ◽  
Open Chest

The effects of heart rate (HR) on myocardial contractility in the mouse heart in situ were first investigated in open-chest mice (n = 7) by left ventricular (LV) catheter-tip micromanometry. HR was first slowed with a sinus node inhibitor (zatebradine), and atrial pacing to progressively increase the HR caused a positive inotropic response (assessed by maximum positive first derivative of LV pressure, LV dP/dtmax) up to a HR of 282 beats/min with the onset of a descending limb of the force-frequency relation (FFR) at 332 beats/min. beta-Adrenergic receptor stimulation (dobutamine) shifted upward and significantly steepened the positive FFR and increased HR at the onset of the descending limb to 402 beats/min. HR and LV dP/dtmax were then studied in closed-chest mice without pacing during recovery from anesthesia (n = 7), and during rest and intermittent physical activity the FFR was linear and positive up to 600 beats/min. HR was then progressively slowed with zatebradine, and the points at rest and during activity fell on the same linear relation. Thus we conclude the following: 1) in the open-chest anesthetized mouse, a positive FFR was amplified by beta-adrenergic receptor stimulation, and 20 in the mouse recovering from anesthesia the sinus node rate remained a critical determinant of myocardial contractility, without a descending limb of the FFR.

Renin-angiotensin system and sympathetic nervous system in cardiac pressure-overload hypertrophy

2000 ◽  
Vol 279 (6) ◽  
pp. H2797-H2806 ◽  
Author(s):  
Wendell S. Akers ◽  
Andrew Cross ◽  
Robert Speth ◽  
Linda P. Dwoskin ◽  
Lisa A. Cassis
Keyword(s):  
Left Ventricle ◽  
Adrenergic Receptor ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Receptor Density ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Sympathetic Nervous

Angiotensin II and norepinephrine (NE) have been implicated in the neurohumoral response to pressure overload and the development of left ventricular hypertrophy. The purpose of this study was to determine the temporal sequence for activation of the renin-angiotensin and sympathetic nervous systems in the rat after 3–60 days of pressure overload induced by aortic constriction. Initially on pressure overload, there was transient activation of the systemic renin-angiotensin system coinciding with the appearance of left ventricular hypertrophy ( day 3). At day 10, there was a marked increase in AT1 receptor density in the left ventricle, increased plasma NE concentration, and elevated cardiac epinephrine content. Moreover, the inotropic response to isoproterenol was reduced in the isolated, perfused heart at 10 days of pressure overload. The affinity of the β2-adrenergic receptor in the left ventricle was decreased at 60 days. Despite these alterations, there was no decline in resting left ventricular function, β-adrenergic receptor density, or the relative distribution of β1- and β2-receptor sites in the left ventricle over 60 days of pressure overload. Thus activation of the renin-angiotensin system is an early response to pressure overload and may contribute to the initial development of cardiac hypertrophy and sympathetic activation in the compensated heart.

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