Decreased cardiac response to isoproterenol infusion in acute and chronic hypoxia

The hypothesis of a blunted chronotropic response of cardiac beta-adrenergic receptors in altitude hypoxia was tested in nine subjects at sea level (SL) by infusion of isoproterenol. Observations were made at SL, in acute hypoxia (2 days at 4,350 m, condition H1), in more prolonged hypoxia [13 days between 850 and 4,800 m, condition H2] and in chronic hypoxia [21 days at 4,800 m, condition H3]. Resting heart rate was higher in all hypoxic conditions. Resting norepinephrine concentrations were found to be significantly higher in conditions H2 (1.64 +/- 0.59) and H3 (1.74 +/- 0.76) than at SL (0.77 +/- 0.18 ng/ml). Isoproterenol, diluted in saline, was infused at increasing doses of 0.0, 0.02, 0.04, and 0.06 micrograms.kg-1.min-1. For the highest dose, there was a significantly smaller increase in heart rate in conditions H1 (35 +/- 9), H2 (33 +/- 11), and H3 (31 +/- 11) than at SL (45 +/- 8 min-1). The increase in pulse (systolic/diastolic) pressure, considered as the vascular response to isoproterenol infusion, was smaller in condition H3 (29 +/- 16) than at SL (51 +/- 24 mmHg). There was a significant increase in the dose of isoproterenol required to increase heart rate by 25 min-1 and decrease in slope of heart rate increase vs. log(dose) relationship in conditions H2 and H3. Thus an hypoxia-related attenuated response of beta-adrenergic receptors to exogenous stimulation was found in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text

Effect of exercise duration on density and coupling of beta-adrenergic receptors on human mononuclear cells

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.3.1494 ◽

1989 ◽

Vol 66 (3) ◽

pp. 1494-1500 ◽

Cited By ~ 22

Author(s):

M. J. Frey ◽

D. Mancini ◽

D. Fischberg ◽

J. R. Wilson ◽

P. B. Molinoff

Keyword(s):

Heart Rate ◽

Adrenergic Receptors ◽

Regulatory Protein ◽

Nucleotide Binding ◽

Plasma Norepinephrine ◽

Base Line ◽

Guanine Nucleotide ◽

Beta Adrenergic Receptors ◽

Beta Adrenergic ◽

Guanine Nucleotide Binding

The effect of maximal exercise on lymphocyte beta-adrenergic receptors was examined in 26 normal subjects. Exercise increased O2 consumption (Vo2) from 5 +/- 1 to 50 +/- 4 ml.min-1.kg-1, plasma norepinephrine level from 188 +/- 28 to 2,682 +/- 160 pg/ml, and plasma epinephrine level from 94 +/- 72 to 857 +/- 180 pg/ml. The density of beta-adrenergic receptors on lymphocytes obtained at rest was 31 +/- 3.7 fmol/mg protein; exercise increased the density of receptors by 86 +/- 33% (range 0–257%) to 58.3 +/- 1.5 fmol/mg protein but did not alter the affinity of the receptor for [125I]iodopindolol or the coupling of the receptor to the guanine nucleotide-binding regulatory protein. The density of beta-adrenergic receptors increased progressively throughout exercise and paralleled the increase in heart rate. The magnitude of the change in the density of beta-adrenergic receptors did not correlate with the magnitude of the increase in heart rate, Vo2, or plasma levels of catecholamines. The density of receptors was still elevated 15 min after completion of exercise but fell below base line 1 h after peak exercise to 18.2 +/- 6.7 fmol/mg protein (P less than 0.05 vs. base-line levels). These results demonstrate that exhaustive exercise results in a progressive increase in the number of beta-adrenergic receptors on lymphocyte membranes, followed by a reduction in the density of receptors during the recovery phase of exercise. Despite a significant increase in the level of plasma catecholamines, the receptor remains coupled to the guanine nucleotide-binding regulatory protein.

Download Full-text

Beta-adrenergic receptors predict heart rate reactivity to a psychosocial stressor.

Psychosomatic Medicine ◽

10.1097/00006842-199011000-00003 ◽

1990 ◽

Vol 52 (6) ◽

pp. 621-623 ◽

Cited By ~ 24

Author(s):

P J Mills ◽

J E Dimsdale ◽

M G Ziegler ◽

C C Berry ◽

R D Bain

Keyword(s):

Heart Rate ◽

Adrenergic Receptors ◽

Beta Adrenergic Receptors ◽

Psychosocial Stressor ◽

Heart Rate Reactivity ◽

Beta Adrenergic

Download Full-text

Effects of hypoxia on density of beta-adrenergic receptors

Journal of Applied Physiology ◽

10.1152/jappl.1981.50.2.363 ◽

1981 ◽

Vol 50 (2) ◽

pp. 363-366 ◽

Cited By ~ 86

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.

Download Full-text

Regulation of atrial autonomic receptors in experimental cyanotic heart disease

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.261.4.h1135 ◽

1991 ◽

Vol 261 (4) ◽

pp. H1135-H1140 ◽

Cited By ~ 2

Author(s):

R. Doshi ◽

E. Strandness ◽

D. Bernstein

Keyword(s):

Heart Rate ◽

Adrenergic Receptors ◽

Receptor Subtypes ◽

Receptor Density ◽

Beta Adrenergic Receptors ◽

Beta Adrenergic ◽

Beta 2 ◽

The Right ◽

Chronic Hypoxemia ◽

Inotropic Responses

During chronic hypoxemia, left ventricular beta-adrenergic receptor density is decreased and a dissociation occurs between increased chronotropic and decreased inotropic responses to chronically elevated sympathetic tone. To determine whether this dissociation was related to alterations in autonomic receptor populations in the right atrium, we studied right atrial cholinergic and beta-adrenergic receptors in chronically hypoxemic newborn lambs and in normoxemic controls. Heart rate response was determined by infusing isoproterenol at 0.1 or 0.5 microgram.kg-1.min-1. Muscarinic receptors were quantified with [3H]quinuclidinyl benzilate and beta-adrenergic receptors with [125I]iodocyanopindolol. Competition with ICI 118,551 was used to determine beta 1- vs. beta 2-receptor subtypes. In the hypoxemic lambs, isoproterenol resulted in a lesser percentage increase in heart rate (hypoxemic, 46 +/- 6% vs. control, 89 +/- 17%, P less than 0.05); however, because baseline heart rate was higher in the hypoxemic lambs (213 +/- 7 vs. 177 +/- 12 beats/min, P less than 0.05), maximal heart rate responses were similar (310 +/- 7 vs. 326 +/- 6 beats/min, NS). There was no change in receptor density or affinity of either muscarinic or beta-adrenergic receptors and no change in the proportion of beta 1- vs. beta 2-receptor subtypes. Thus the dissociation between the chronotropic and inotropic responses to chronic hypoxemia may be in part secondary to a differential regulation of beta-adrenergic receptors between the left ventricle and the right atrium.

Download Full-text

Autonomic nervous control of heart rate in muskrats during exercise in air and under water.

Journal of Experimental Biology ◽

10.1242/jeb.199.7.1563 ◽

1996 ◽

Vol 199 (7) ◽

pp. 1563-1568 ◽

Cited By ~ 5

Author(s):

P E Signore ◽

D R Jones

Keyword(s):

Heart Rate ◽

Neural Control ◽

Cardiac Response ◽

Resting Heart Rate ◽

Adrenergic Stimulation ◽

Beta Adrenergic ◽

Pronounced Increase ◽

Chronotropic Response ◽

Autonomic Nervous ◽

Parasympathetic Tone

Neural control of the cardiac responses to exercise in air (running) and under water (diving) was studied in the muskrat (Ondatra zibethicus) by means of acute pharmacological blockade with the muscarinic blocker atropine and the beta-adrenergic blocker nadolol. Saline injection was used as a control. Controls running on a treadmill showed a marked increase in heart rate with exercise. Atropine-treated animals had a higher resting heart rate than controls, but heart rate still increased with running. Nadolol-treated animals had a lower resting heart rate than controls and displayed a less pronounced increase in heart rate with running than controls. Animals treated with a combination of atropine and nadolol had a resting heart rate similar to that of controls but their heart rate was unaffected by running. Thus, exercise tachycardia in muskrats is due to activation of the sympathetic system and also to a reduction in parasympathetic tone. Heart rate decreased markedly during voluntary submergence in controls but rose as muskrats swam submerged against increasing water flows. Nevertheless, diving bradycardia was still present. Free-diving bradycardia and the relative increase in heart rate with underwater exercise were abolished by atropine and unaffected by nadolol. Hence, unlike the cardiac response to exercise in air, the cardiac response to underwater exercise is due only to a reduction in parasympathetic tone. Injection of the beta-adrenergic agonist isoproterenol markedly increased heart rate in air but had little effect during voluntary and forced dives, indicating a marked decrease in the sensitivity of cardiac cells to adrenergic stimulation during submergence. These results strongly suggest that accentuated antagonism between the two branches of the autonomic nervous system occurs during diving so that parasympathetic influences on the heart predominate and inhibit any chronotropic response to adrenergic stimulation.

Download Full-text

Beta-adrenergic receptors ventricular and atrial subtypes density and heart rate variability in thyrotoxic hypertrophied rat hearts

Journal of Molecular and Cellular Cardiology ◽

10.1016/0022-2828(89)90897-3 ◽

1989 ◽

Vol 21 ◽

pp. S11

Author(s):

H HAOUALA

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Adrenergic Receptors ◽

Beta Adrenergic Receptors ◽

Beta Adrenergic ◽

Rat Hearts

Download Full-text

Reversal of hypoxia-induced decrease in human cardiac response to isoproterenol infusion

Journal of Applied Physiology ◽

10.1152/jappl.1989.67.2.523 ◽

1989 ◽

Vol 67 (2) ◽

pp. 523-527 ◽

Cited By ~ 27

Author(s):

J. P. Richalet ◽

J. L. Le-Trong ◽

C. Rathat ◽

P. Merlet ◽

P. Bouissou ◽

...

Keyword(s):

Heart Rate ◽

Sea Level ◽

Heart Rate Response ◽

Normal Values ◽

Cardiac Response ◽

Chronotropic Response ◽

Beta Receptors ◽

The Mean ◽

Arterial O2 Saturation ◽

Isoproterenol Infusion

A decrease in heart rate response to isoproterenol (IP) infusion has been previously described in humans exposed to acute (2–3 days) or chronic (21 days) exposure to altitude hypoxia (J. Appl. Physiol. 65: 1957–1961, 1988). To evaluate this cardiac response in subacute (8 days) hypoxia and to explore its reversal with restoration of normoxia, six subjects received an IP infusion under normoxia (condition N), after 8 days in altitude (4,350 m, condition H8), on the same day in altitude after inhalation of O2 restoring normoxic arterial O2 saturation (SaO2, condition HO), and 6–11 h (condition RN) and 4–5 mo (condition ND) after the return to sea level. Cardiac chronotropic response to IP, evaluated by the mean increase in heart rate from base value (delta HR, min-1), was lower in condition H8 [mean 30 +/- 13 (SD)] than in condition N (50 +/- 14, P less than 0.03); it was slightly higher in condition HO (38 +/- 14) or condition RN (42 +/- 15) than condition H8 but still significantly different from condition N (P less than 0.03), despite normal values of SaO2. delta HR in condition ND (55 +/- 10) returned to base N value. These findings confirm the hypothesis of a hypoxia-induced decrease in cardiac chronotropic function. Two possible mechanisms are suggested: an O2-dependent one, rapidly reversible with recent restoration of normoxia, and a more slowly reversible mechanism, probably a downregulation of the cardiac beta-receptors.

Download Full-text

Exercise-induced functional desensitization of canine cardiac beta-adrenergic receptors

Journal of Applied Physiology ◽

10.1152/jappl.1987.62.4.1721 ◽

1987 ◽

Vol 62 (4) ◽

pp. 1721-1723 ◽

Cited By ~ 25

Author(s):

D. B. Friedman ◽

G. A. Ordway ◽

R. S. Williams

Keyword(s):

Heart Rate ◽

Adrenergic Receptors ◽

Treadmill Running ◽

Strenuous Exercise ◽

Beta Adrenergic Receptors ◽

Similar Reduction ◽

Beta Adrenergic ◽

Single Bout ◽

Chronotropic Effects ◽

Exercise Induced

To test the hypothesis that the high levels of endogenous catecholamines associated with strenuous exercise produce functional desensitization of cardiac beta-adrenergic receptors, we measured the bolus chronotropic dose of isoproterenol necessary to produce a 25-beats/min increase in heart rate (CD25) in the resting state and after the return of heart rate to resting levels after 60 min of treadmill running in 13 normal dogs. Immediately after exercise, 12 of 13 dogs were less sensitive to the chronotropic effects of beta-adrenergic receptor stimulation: mean CD25 increased from 1.16 +/- 0.17 to 3.50 +/- 0.98 micrograms (P less than 0.02). A similar reduction in isoproterenol sensitivity was evident regardless of whether testing was performed in the presence or absence of vagal blockade with atropine. By 3 h after exercise, CD25 had returned to the preexercise level, with no further change noted 24 h after exercise. There was no change in the CD25 when measured serially in three unexercised dogs. We conclude that a single bout of dynamic exercise is sufficient to produce a significantly decreased chronotropic responsiveness to isoproterenol. This phenomenon may represent an acute but transient desensitization of cardiac beta-adrenergic receptors.

Download Full-text