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.

Beta-receptors and adenylate cyclase: comparison of nonischemic, ischemic, and postmortem tissue

1990 ◽  
Vol 258 (1) ◽  
pp. H140-H144 ◽  
Author(s):  
D. E. Vatner ◽  
M. A. Young ◽  
D. R. Knight ◽  
S. F. Vatner
Keyword(s):  
Adenylate Cyclase ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Striking Similarity ◽  
Receptor Density ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic

We compared the effects of myocardial ischemia and postmortem changes on beta-adrenergic receptors and their coupling to adenylate cyclase activity. The effects of 1 h of left circumflex coronary artery occlusion were examined in eight conscious calves, which were then anesthetized with pentobarbital sodium, and the left ventricle was divided into nonischemic and ischemic regions. A crude membrane fraction was prepared from each region and from the nonischemic tissue 1 h postmortem. beta-Adrenergic receptor density increased (152 +/- 55%) and decreases in basal (-21 +/- 6.1%), isoproterenol-stimulated (-25 +/- 8.0%), 5'-guanylylimidodiphosphate [Gpp(NH)p]-stimulated (-17 +/- 5.8%), fluoride-stimulated (-26 +/- 5.8%), and forskolin-stimulated (-31 +/- 8.4%) adenylate cyclase activities were observed in the ischemic myocardium compared with nonischemic myocardium. Similarly, in postmortem samples, beta-adrenergic receptor density rose 58 +/- 16%, whereas decreases in basal (-48 +/- 8.7%), isoproterenol-stimulated (-61 +/- 7.8%), Gpp(NH)p-stimulated (-58 +/- 7.0%), fluoride-stimulated (-64 +/- 6.1%), and forskolin-stimulated (-52 +/- 6.2%) adenylate cyclase activities were observed. Agonist-binding competition curves with isoproterenol were shifted, indicating that beta-adrenergic receptors were binding agonists with low affinity in both the ischemic and postmortem myocardium. The marked, but directionally opposite, changes in receptor density and adenylate cyclase that occur postmortem indicate the importance of prompt processing of tissues. The striking similarity in response of beta-adrenergic receptor agonist and antagonist binding and adenylate cyclase activity in ischemic and postmortem tissue raises the speculation that similar mechanisms may operate under both conditions.

Effects of coronary arterial reperfusion on beta-adrenergic receptor-adenylyl cyclase coupling

1993 ◽  
Vol 264 (1) ◽  
pp. H196-H204 ◽  
Author(s):  
D. E. Vatner ◽  
K. Kiuchi ◽  
W. T. Manders ◽  
S. F. Vatner
Keyword(s):  
Adenylyl Cyclase ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Cyclase Activity ◽  
Receptor Density ◽  
Beta Adrenergic Receptors ◽  
Adenylyl Cyclase Activity ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
High Affinity

The effects of 1 h of coronary arterial occlusion (CAO) followed by 15 min reperfusion (CAR) were examined in nine conscious dogs. Ischemia was verified by decreased regional blood flow (radioactive microspheres) and loss of systolic regional wall motion in the ischemic zone. beta-Adrenergic receptor density assessed by 125I-labeled cyanopindolol binding in a crude membrane fraction tended to decrease but was not significantly different. However, adenylyl cyclase activity and the guanine nucleotide stimulatory protein (Gs) were reduced in ischemic subendocardium compared with nonischemic subendocardium. The fraction of beta-adrenergic receptors binding agonist with high affinity increased in ischemic subendocardial and subepicardial layers. Compared with prior data in experiments with 1 h CAO without CAR, the increase in beta-adrenergic receptor density that occurs with myocardial ischemia is rapidly reversed with CAR of 15 min duration, while the decreased fraction of receptors binding agonist with high affinity was reversed to an increase in high-affinity receptors. The global decreases in adenylyl cyclase and Gs, which have been observed with simple CAO, persist but are observed selectively in the previously ischemic subendocardium after CAR. Thus both CAO and CAR affect beta-adrenergic receptors and adenylyl cyclase differently. During CAR, increased numbers of beta-adrenergic receptors binding agonist with high affinity occur potentially as a compensatory mechanism in the face of persistent reductions in adenylyl cyclase activity and Gs.

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)

scholarly journals Thyroid-hormone modulation of the number of β-adrenergic receptors in rat fat-cell membranes

1978 ◽  
Vol 176 (3) ◽  
pp. 1007-1010 ◽  
Author(s):  
Y Giudicelli
Keyword(s):  
Thyroid Hormone ◽  
Binding Sites ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Receptor Density ◽  
Beta Adrenergic Receptors ◽  
Fat Cell ◽  
Beta Adrenergic ◽  
Hormone Modulation ◽  
Β Adrenergic Receptors

Adipocytes from thyroidectomized rats contain 3 times less [3H]dihydroalprenolol-binding sites (beta-adrenergic receptors) than adipocytes from euthyroid animals. This alteration is not solely due to cell-size differences, but also to a thyroidectomy-induced defect in beta-adrenergic receptor density per adipocyte surface area, a defect that is furthermore corrected by tri-iodothyronine treatment.

Hepatic sexual dimorphism: ontogeny and influence of adult gonadectomy

1989 ◽  
Vol 256 (3) ◽  
pp. E392-E400
Author(s):  
R. K. Studer ◽  
L. Ganas
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Female Rats ◽  
Adenylate Cyclase System ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic Receptor ◽  
Intact Cells ◽  
Beta Adrenergic ◽  
Receptor Concentration ◽  
Males And Females

The ontogeny of alpha 1- and beta-adrenergic receptors and their relative stimulation of phosphorylase alpha activity in hepatic tissue from male and female rats were compared. A decrease in beta-adrenergic receptor concentration and 4-(t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidazol-2-one HCl affinity for these sites was found in males and females, when data from membranes of 20- to 22-day animals was compared with that from neonates. No subsequent decline in receptor concentration was noted in the female; however, the beta-mediated phosphorylase activation was further diminished by 49-56 days, suggesting maturational changes beyond the receptor-adenylate cyclase system. Although high-affinity beta-adrenergic receptors were documented in membranes from pubertal males, they were not identified on the intact cells, and activation of phosphorylase alpha via the beta-pathway was minimal. This suggests the majority of the beta-receptors are sequestered in cellular sites not accessible to the hydrophilic ligand or epinephrine in the sexually mature male. Ontogeny of the alpha 1-adrenergic receptors was similar in males and females. Gonadectomy of mature males and females did not eliminate the sexual differences in adrenergic response. However, the ovariectomized females developed an enhanced basal and alpha-adrenergic stimulated phosphorylase activity. The rise in cytosolic free calcium in response to epinephrine was increased in the ovariectomized females to values seen in the intact male, whereas the response in the castrate male was depressed. The results suggest the dimorphism in alpha 1- and beta-adrenergic receptor function is determined by factors other than the ambient concentration of sex steroids in the adult.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of hypoxia on density of beta-adrenergic receptors

1981 ◽  
Vol 50 (2) ◽  
pp. 363-366 ◽  
Author(s):  
N. F. Voelkel ◽  
L. Hegstrand ◽  
J. T. Reeves ◽  
I. F. McMurty ◽  
P. B. Molinoff
Keyword(s):  
High Altitude ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Low Dose ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Altitude Exposure

Exposure to chronic hypoxia results in a lower resting heart rate and a blunted cardiovascular responsiveness to beta-adrenergic receptor stimulation. Possible effects of acclimatization to high altitude on the binding of [125I]iodohydroxybenzylpindolol to beta-adrenergic receptors on membranes of right and left ventricles of rat heart were determined. Chronic high-altitude exposure led to a decrease in the density of beta-adrenergic receptors in nonhypertrophied left ventricles as well as in hypertrophied right ventricles. The affinity of the receptor for the radioligand was not changed by the exposure to high altitude, suggesting that the properties of the receptor were not affected. Basal and isoproterenol-stimulated adenylate cyclase activities were decreased in membranes prepared from hearts and pulmonary arteries of rats acclimatized to high altitude. The loss of cardiac beta-adrenergic receptors in rats adapted to high altitude was prevented by the chronic coadministration of a low dose of DL-propranolol. The results suggest that changes in beta-adrenergic receptor density may partially explain the hemodynamic adaptation that occurs with chronic hypoxia. These decreases may be due to a loss of functional beta-adrenergic receptors caused by chronically elevated concentrations of circulating neurally released catecholamines.

Refined membrane preparations mask ischemic fall in myocardial beta-receptor density

1989 ◽  
Vol 257 (3) ◽  
pp. H1032-H1036
Author(s):  
A. A. Wolff ◽  
D. K. Hines ◽  
J. S. Karliner
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Coronary Occlusion ◽  
Acute Ischemia ◽  
Receptor Density ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Use Of Data ◽  
H2 Receptors ◽  
Myocardial Membrane

Most of the previous studies of ischemic myocardial beta-adrenergic receptors have employed membrane preparations in which the initial pellet from the myocardial homogenate spun at a low speed was discarded. We studied changes in beta-adrenergic receptor density ([125I]-iodocyanopindolol; Bmax) during 30 min of coronary occlusion in surgically anesthetized open-chest rabbits using just such a pellet [homogenized heart spun at 1,000 g (1,000-g pellet)], as well as a second pellet from the supernatant of the first pellet [spun at 40,000 g (40,000-g pellet)]. Bmax fell during acute ischemia in the 1,000-g pellet [46.8 +/- 6.1 vs. 21.6 +/- 2.4 (SE) fmol/mg protein; P less than 0.01; n = 7] but did not change in the 40,000-g pellet [46.8 +/- 6.5 vs. 47.9 +/- 2.6 (SE) fmol/mg protein; P = NS; n = 6]. The 1,000-g pellet contained 70.0 +/- 8.1% of the beta-adrenergic receptors measured between the two preparations (P less than 0.05; n = 8) and all of the histamine H2-receptors; therefore, to minimize receptor loss and other potential artifacts, unspun myocardial homogenate was studied. An ischemic decrease in Bmax was still observed [32.9 +/- 2.0 vs. 20.9 +/- 4.1 (SE) fmol/mg protein; P less than 0.05; n = 5]. These results support the use of data from cruder myocardial membrane preparations (e.g., 1,000-g pellet or unspun homogenate), which may be of greater pathophysiological relevance than data derived from a standard more-refined preparation (40,000-g pellet).

Triiodothyronine Increases Contractility Independent of β-Adrenergic Receptors or Stimulation of Cyclic-3',5'-Adenosine Monophosphate

1995 ◽  
Vol 82 (4) ◽  
pp. 1004-1012. ◽  
Author(s):  
Douglas G. Ririe ◽  
John F. IV Butterworth ◽  
Roger L. Royster ◽  
Drew A. MacGregor ◽  
Gary P. Zaloga
Keyword(s):  
Thyroid Hormones ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Adenosine Monophosphate ◽  
Left Ventricular ◽  
Camp Production ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Inotropic Effects ◽  
Isolated Rat

Background Triiodothyronine regulates cardiac contractility; however, the mechanisms by which it produces its acute contractile effects remains unknown. We compared the acute effects of thyroid hormones (triiodothyronine [T3] and thyroxine [T4]) and of isoproterenol on the contractility of isolated rat hearts. In addition, we sought to determine whether the acute inotropic effects of thyroid hormones were mediated by beta-adrenergic receptors or by increased production of cyclic-3',5'-adenosine monophosphate (cAMP). Methods A Langendorff heart preparation harvested from euthyroid male Sprague-Dawley rats was used. Drugs were administered through an aortic perfusion catheter. A pressure-transduced left-ventricular balloon catheter measured pressure and heart rate changes. Changes in the maximum positive rate of change in pressure (dP/dT) and maximum negative dP/dT were determined. Responses to varying doses of T3, T4, and isoproterenol were assessed in the presence and absence of beta-adrenergic receptor blockade with propranolol. cAMP production, measured by radioimmunoassay, was determined in myocardial cell suspensions after incubation with T3 or isoproterenol. Results T3 0.74 nmol rapidly and significantly increased maximum dP/dT by 335 +/- 38 mmHg/s within 30 s after bolus injection; however, contractility was unchanged after as much as 12.9 nmol T4. The maximal increase in dP/dT after 0.8 nmol isoproterenol was comparable to that produced by T3. However, the cardiotonic actions of isoproterenol were significantly slower to develop (peaking at 60 vs. 15 s) and lasted longer than those of T3. Pretreatment with propranolol 1 mumol diminished the contractile effects of isoproterenol but had no effect on those of T3. Concentrations of isoproterenol that increase contractility also significantly increased cAMP production in isolated rat myocardial cells. However, T3 failed to increase cAMP production. Conclusions These results demonstrate that the acute inotropic effects of T3 are not shared by T4 and appear unrelated to beta-adrenergic receptor mechanisms or to generation of cAMP. Thus, T3 acutely stimulates cardiac contraction by mechanisms that differ from those of the more commonly used beta-adrenergic receptor agonists and phosphodiesterase inhibitors. Further studies are needed to identify the mechanisms underlying the acute contractile effects of T3 and to determine whether T3 will prove useful for increasing ventricular function in patients.

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