Enhanced beta-adrenergic-receptor responsiveness in hypoxic neonatal pulmonary circulation

1981 ◽  
Vol 240 (5) ◽  
pp. H697-H703 ◽  
Author(s):  
J. E. Lock ◽  
P. M. Olley ◽  
F. Coceani
Keyword(s):  
Pulmonary Circulation ◽  
Beta Blockade ◽  
Base Line ◽  
Pulmonary Resistance ◽  
Beta Adrenergic ◽  
Beta Receptor ◽  
Adrenergic Activity ◽  
Alpha Blockade ◽  
Alveolar Hypoxia ◽  
Constrictor Response

The influence of alveolar hypoxia on pulmonary vascular adrenergic receptors was studied in conscious newborn lambs. In control animals, pulmonary vessels were directly constricted by epinephrine and norepinephrine, but were unaffected by isoproterenol. Pulmonary resistance (PVR) was also unaffected by propranolol, thus implying minimal beta-receptor activity under normoxic conditions. Hypoxia raised PVR but also modified the pulmonary vascular responses to catecholamines: isoproterenol became a dilator, whereas the constrictor effects of epinephrine and norepinephrine were abolished. Although beta-blockade did not alter base-line PVR, propranolol increased the constrictor response to hypoxia, implying that hypoxia increases beta-adrenergic activity or reactivity in the pulmonary circulation. Consistent with this hypothesis are the following: 1) in alpha-blocked lambs, epinephrine was without local effects during normoxia, but caused vasodilation during hypoxia; 2) the absent constrictor response to epinephrine during hypoxia is fully restored by propranolol; and 3) although alpha-blockade blunts the hypoxic constrictor response, the full response is restored when beta-blockade is added. These results indicate that the hypoxic constrictor response is partially opposed by increased beta-mediated vasodilation. These enhanced beta-receptor effects are due, at least in part, to increased beta-receptor reactivity of unknown mechanism.

Physiological insulin action is opposed by beta-adrenergic mechanisms in dogs

1988 ◽  
Vol 255 (1) ◽  
pp. E33-E40 ◽  
Author(s):  
G. A. Werther ◽  
S. Joffe ◽  
R. Artal ◽  
M. A. Sperling
Keyword(s):  
Insulin Infusion ◽  
Glucose Production ◽  
Beta Blockade ◽  
Base Line ◽  
Adrenergic Blockade ◽  
Hormonal Changes ◽  
Beta Adrenergic ◽  
Adrenergic Mechanisms ◽  
Alpha Blockade

To investigate the possible role of adrenergic mechanisms in modulating glucose homeostasis during physiological insulin changes, we studied the effects of alpha-, beta-, or combined alpha- and beta-adrenergic blockade on glucose production (Ra) and utilization (Rd) via isotope ([3-(3)H]glucose) dilution during nonstressful, nonhypoglycemic conditions in response to physiological insulin changes in conscious dogs. Without adrenergic blockade, infusion of insulin at 0.275 mU.kg-1.min-1 (control) caused glucose to fall from 92 +/- 4 to 82 +/- 4 mg/dl over 30 min, because of transient fall in Ra from 2.8 +/- 0.4 to 2.3 +/- 0.3 mg.kg-1.min-1, which recovered to base line by 30 min. There was a later rise in Rd to 3.9 +/- 0.4 mg.kg-1.min-1 at 45 min, but no counter-regulatory hormonal changes (glucagon, cortisol, epinephrine, and norepinephrine) to account for these findings in glucose kinetics. alpha-Blockade alone led to an initial rise in base-line insulin and consequent fall in glucose, associated with a transient fall in Ra but no change in Rd; infusion of insulin led to a further small fall in glucose, with no change in Ra, but with a rise at 30 min in Rd similar to controls. beta-Blockade alone led to an initial fall in insulin and modest rise in glucose; insulin infusion led to a greater rate of fall in glucose than in controls (from 112 +/- 6 to 78 +/- 7 mg/dl over 30 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of beta-adrenergic agents in lungs of normal and air-embolized awake sheep

1988 ◽  
Vol 64 (6) ◽  
pp. 2647-2652 ◽  
Author(s):  
M. R. Bonsignore ◽  
E. H. Jerome ◽  
P. L. Culver ◽  
P. M. Dodek ◽  
N. C. Staub
Keyword(s):  
Air Embolism ◽  
Lymph Flow ◽  
Beta Agonist ◽  
Beta Blockade ◽  
Base Line ◽  
Pulmonary Hemodynamics ◽  
Beta Adrenergic ◽  
Adrenergic Agents ◽  
Venous Air Embolism ◽  
Lung Lymph

It is unclear whether beta-adrenergic agonists or antagonists affect lung liquid and protein exchange by changing pulmonary hemodynamics or microvascular leakiness. In 23 unanesthetized, instrumented sheep with long-term lung lymph fistulas, we assessed the effect of the beta-agonist terbutaline or the beta-antagonists propranolol, nadolol, and atenolol, all infused intravenously, on lung lymph flow under base-line conditions and during the acute lung injury caused by 4 h of venous air embolism. Under base-line conditions, neither beta-stimulation nor blockade had any effect. During air embolism, terbutaline decreased pulmonary vascular resistance and lymph flow by 25%. Propranolol and nadolol (non-selective beta 1,beta 2-antagonists) but not atenolol (selective beta 1-antagonist) also decreased lymph flow by 22% on average. We favor the more conservative (hemodynamic) over the more liberal (altered permeability) explanation for our results. First, beta-stimulation clearly caused vasodilation, which lowered the pulmonary microvascular pressure at the site of injury. beta-blockade caused changes similar to alpha-stimulation (J. Appl. Physiol. 62: 2147–2153, 1987). We therefore interpret the beta-blockade as unmasking pulmonary arterial alpha-receptors stimulated by the air-embolism injury, thus allowing vasoconstriction upstream to the site of injury. We do not believe the explanation of the beta-agent effects requires any modulation of lung microvascular leakiness by beta-adrenergic agents.

Pulmonary vascular reactivity to biogenic amines during acute hypoxia

1988 ◽  
Vol 255 (2) ◽  
pp. H329-H334 ◽  
Author(s):  
R. J. Porcelli ◽  
M. V. Cutaia
Keyword(s):  
Biogenic Amines ◽  
Adrenergic Receptor ◽  
Vascular Reactivity ◽  
Acute Hypoxia ◽  
Receptor Activity ◽  
Beta Blockade ◽  
Beta Activity ◽  
Base Line ◽  
Pressor Responses ◽  
Alpha Blockade

The effects of acute hypoxia on the pressor responses to five biogenic amines were studied in isolated blood-perfused cat lungs. Hypoxia (Po2 = 46 +/- 2 Torr) reduced the pressor responses to phenylephrine while changing the pressor responses to epinephrine and norepinephrine to vasodilation. Hypoxia reduced the pressor responses to histamine, and these reductions were preceded by small but significant vasodilations. Hypoxia had no effect on the pressor responses to serotonin. These changes in pulmonary vasoactivity were reversed on reoxygenation, independent of changes in base-line tone and not correlated with circulating catecholamines. We also examined the effects of hypoxia on the pressor responses to norepinephrine during beta-blockade with propranolol and then alpha-blockade with dibenzyline. The vasodilation produced during hypoxia by norepinephrine was blocked by propranolol, and vasoconstriction reappeared. When alpha-blockade was then established, vasodilation to norepinephrine reemerged during hypoxia. These results demonstrate that hypoxia produces changes in pulmonary vascular responsiveness that are acute in nature and reversible. Although the cellular nature of these changes is unknown, the data suggest that hypoxia produces acute shifts in antagonistic adrenergic receptor activity by either 1) reducing alpha- or increasing beta-receptor activity or 2) acutely changing adrenergic receptor conformation, affinity, or efficacy, such that beta-activity prevails.

Adrenoreceptor effects on rat muscle blood flow during treadmill exercise

1987 ◽  
Vol 62 (4) ◽  
pp. 1465-1472 ◽  
Author(s):  
M. H. Laughlin ◽  
R. B. Armstrong
Keyword(s):  
Blood Flow ◽  
Muscle Fiber ◽  
Treadmill Exercise ◽  
Fiber Type ◽  
Muscle Blood Flow ◽  
Beta Blockade ◽  
Beta Receptor ◽  
Extensor Muscles ◽  
Alpha Blockade ◽  
Total Muscle

The purpose of this study was to examine the effects of the adrenergic receptors on the distribution of blood flow within and among skeletal muscles in rats. Blood flow was measured with the radiolabeled microsphere technique before exercise and during treadmill exercise at 15 or 60 m/min. Alpha- (phentolamine) or beta- (propranolol) adrenergic blocking drugs were administered, and then blood flow was measured and results compared with those from saline-treated rats. Before exercise, alpha-blockade caused increases in total muscle blood flow and in all fast-twitch muscles, whereas muscles composed of greater than 20% slow-twitch fibers showed no effect. During exercise at 15 m/min, the normal increase in total muscle blood flow was attenuated by alpha-blockade. Compared with controls, blood flow was less in the high-oxidative (fast and slow) muscle fiber areas of extensor muscles, whereas blood flow to white areas of extensor muscles was increased. beta-Blockade tended to decrease muscle blood flow before exercise and during exercise at 15 m/min with no apparent relationship between the effects of blockade on blood flow and muscle fiber type. These effects of beta-blockade were not apparent during exercise at 60 m/min. We conclude that before exercise alpha-receptor effects are limited to fast muscle, whereas beta-receptor influences are independent of fiber type, beta-receptors contribute to the initial hyperemia of exercise at 15 m/min, and beta-receptor influence is inversely related to metabolic rate.

The effect of alveolar hypoxia on pulmonary vascular responsiveness in the conscious newborn lamb

1980 ◽  
Vol 58 (2) ◽  
pp. 153-159 ◽  
Author(s):  
James E. Lock ◽  
Francis Hamilton ◽  
Peter M. Olley ◽  
Flavio Coceani
Keyword(s):  
Pulmonary Circulation ◽  
Vascular Tone ◽  
High Dose ◽  
Base Line ◽  
Vascular Effects ◽  
Maximal Dilatation ◽  
Newborn Lamb ◽  
Vascular Responsiveness ◽  
Alveolar Hypoxia ◽  
Induced Changes

To determine the effect of alveolar hypoxia and consequent increased pulmonary vascular tone on the responsiveness of the neonatal pulmonary circulation, we studied the local pulmonary vascular effects of acetylcholine, bradykinin, and histamine in the normoxic and hypoxic newborn lamb. Right and left pulmonary flows were continuously monitored from chronically implanted electromagnetic flow probes, agents were injected into only one lung, and changes in the proportion of pulmonary blood flow directed to the injected lung (Qinj/QT) provided a measure of active local pulmonary vascular constriction or dilation. At maximally tolerated doses, hypoxia enhanced the dilatory effects of acetylcholine and diminished the constrictor effects of histamine but hypoxia had a minimal effect on the maximal dilatation induced by bradykinin. Hypoxia did appear to lower the threshold dose for bradykinin's effects.These results demonstrate that base-line conditions may qualitatively alter the responsiveness of the neonatal pulmonary circulation to several drugs. In these agents, increased base-line tone generally augmented dilatory effects and diminished constrictor effects. However, the lack of such an effect on the dilator response to a high dose of bradykinin suggests the possibility that hypoxic-induced changes in pulmonary vascular responsiveness may not be entirely passive. Further, these results do not support the hypothesis that hypoxic-induced vasoconstriction is mediated by decreased production of bradykinin.

Effect of Renal Beta- and Alpha-Adrenergic Stimulation on Proximal Sodium Reabsorption in Dogs

1972 ◽  
Vol 43 (4) ◽  
pp. 569-576 ◽  
Author(s):  
L. M. Blendis ◽  
R. B. Auld ◽  
E. A. Alexander ◽  
N. G. Levinsky
Keyword(s):  
Beta Blockade ◽  
Sodium Reabsorption ◽  
Adrenergic Stimulation ◽  
Urine Sodium ◽  
Beta Adrenergic ◽  
Acid Clearance ◽  
Urine Sodium Excretion ◽  
Clearance Studies ◽  
Single Nephron ◽  
Alpha Blockade

1. Micropuncture studies were performed in dogs to evaluate more directly the suggestion from clearance experiments that alpha-adrenergic stimulation enhances and beta-adrenergic stimulation depresses proximal sodium reabsorption. Experiments were performed during unilateral renal artery infusion of the appropriate drugs in the doses used in previous clearance studies. 2. To study pure beta stimulation, collections were made during alpha blockade with phenoxybenzamine and re-collections during the addition of beta stimulation with isoproterenol. No significant changes were noted in the ratio of inulin concentrations in tubular fluid and plasma (TF/P)In (1·49 ± 0·04 to 1·52 ± 0·05), absolute sodium reabsorption (23 ± 1 to 23 ± 3 nl/min), single nephron glomerular filtration rate (SNGFR) (75 ± 7 to 76 ± 15 nl/min) and the ratio of SNGFR to inulin clearance (SNGFR/CIn) × (106), (2·95 ± 0·4 to 2·65 ± 0·4). 3. To study pure alpha-adrenergic stimulation, collections were made during beta blockade with propranolol and again during the addition of alpha-adrenergic stimulation with nor-adrenaline. There were no significant changes in (TF/P)In (1·50 ± 0·09 to 1·42 ± 0·04), absolute sodium reabsorption (25 ± 7 to 17 ± 4 nl/min), SNGFR (68 ± 13 to 58 ± 10 nl/min) or SNGFR/CIn(× 106) (2·76 ± 0·6 to 2·51 ± 0·5). 4. CIn increased slightly after beta but not after alpha stimulations. p-Aminohippuric acid clearance (CPAH) and urine sodium excretion (UNaV) were not significantly different in either set of studies. 5. We conclude that neither alpha not beta adrenergic stimulation has a significant effect on proximal sodium reabsorption when infused in doses that do not alter renal haemodynamics.

CATECHOLAMINE ANTAGONISM TO OXYTOCIN-INDUCED MILK-EJECTION

1971 ◽  
Vol 68 (1_Suppla) ◽  
pp. S5-S38 ◽  
Author(s):  
Helmuth Vorherr
Keyword(s):  
Receptor Blockade ◽  
Milk Ejection ◽  
Beta Adrenergic ◽  
Beta Receptor ◽  
Beta Receptors ◽  
Alpha Receptors ◽  
Adrenergic Blockers ◽  
Beta Receptor Blockade ◽  
Second Pain ◽  
Stimulation Of

ABSTRACT In lactating rats and rabbits the mode of antagonism of sympathomimetics, angiotensin or pain toward oxytocin-induced milk-ejection was investigated. In rats intra-arterial (intrafemoral) doses of 0.01–0.02 μg or intravenous (iv) doses of 0.1–0.5 μg of either epinephrine, isoproterenol, norepinephrine, angiotensin or 10 μg of phenylephrine injected simultaneously with, or 30 seconds before an oxytocin dose (10 μU intrafemoral, 300 μU iv) greatly inhibited or suppressed the oxytocin response. A 15 second pain stimulus caused moderate inhibition. With alpha-receptor blockade pain, epinephrine, isoproterenol, norepinephrine, phenylephrine and angiotensin inhibition were, respectively, 70%, 75%, 100%, 40%, 0% and 100%. Under beta-receptor blockade the corresponding values were 14%, 40%, 0%, 70%, 100% and 100%; with simultaneous intrafemoral injections neither catecholamine was inhibitory toward oxytocin. In corresponding rabbit experiments approximately 10-fold higher iv drug dosages were applied and similar results were observed. In both species, combined alpha and beta-receptor blockade nearly eliminated the antagonistic actions of sympathomimetics toward oxytocin, whereas angiotensin inhibition persisted unchanged. The results indicate: 1) Mammary myoepithelial cells contain beta-adrenergic receptors but no alpha-receptors; 2) Inhibition of oxytocin-induced milk-ejection by isoproterenol and phenylephrine is meditated through stimulation of myoepithelial beta-receptors (myoepithelial relaxation) and vascular alpha-receptors (vasoconstriction), respectively; 3) Epinephrine and norepinephrine inhibition of milk-ejection is due to stimulation of vascular alpha-receptors and myoepithelial beta-receptors; 4) Angiotensin effects are unrelated to adrenergic receptor mechanisms; 5) Administration of both alpha and beta-adrenergic blockers is desirable for stabilizing the sensitivity of the oxytocin milk-ejection assay preparation against interference from endogenous or exogenous catecholamines; 6) Other than using adrenergic blockers, pharmacologic doses of oxytocin can correct nursing difficulties in animals and man with hyperfunction of the adrenal-sympathetic system.

scholarly journals Haemodynamic advantages of combined alpha-blockade and beta-blockade over beta-blockade alone in patients with coronary heart disease.

BMJ ◽  
1982 ◽  
Vol 285 (6338) ◽  
pp. 325-327 ◽  
Author(s):  
S H Taylor ◽  
B Silke ◽  
G I Nelson ◽  
R C Okoli ◽  
R C Ahuja
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Beta Blockade ◽  
Alpha Blockade

Compounds that increase cAMP prevent ischemia-reperfusion pulmonary capillary injury

1992 ◽  
Vol 72 (2) ◽  
pp. 492-497 ◽  
Author(s):  
W. K. Adkins ◽  
J. W. Barnard ◽  
S. May ◽  
A. F. Seibert ◽  
J. Haynes ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Vascular Permeability ◽  
Vascular Resistance ◽  
Capillary Permeability ◽  
Ischemia Reperfusion ◽  
Receptor Activation ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Beta Receptor ◽  
Pulmonary Capillary

This study evaluated the physiological effects of compounds that increase adenosine 3′,5′-cyclic monophosphate (cAMP) on changes in pulmonary capillary permeability and vascular resistance induced by ischemia-reperfusion (I-R) in isolated blood-perfused rabbit lungs. cAMP was elevated by 1) beta-adrenergic stimulation with isoproterenol (ISO, 10(-5) M), 2) post-beta-receptor stimulation of adenylate cyclase with forskolin (FSK, 10(-5) M), 3) and dibutyryl cAMP (DBcAMP, 1 mM), a cAMP analogue. Vascular permeability was assessed by determining the capillary filtration coefficient (Kf,c), and capillary pressure was measured using the double occlusion technique. The total, arterial, and venous vascular resistances were calculated from measured pulmonary arterial, venous, and capillary pressures and blood flow. Reperfusion after 2 h of ischemia significantly (P less than 0.05) increased Kf,c (from 0.115 +/- 0.028 to 0.224 +/- 0.040 ml.min-1.cmH2O-1.100 g-1). These I-R-induced changes in capillary permeability were prevented when ISO, FSK, or DBcAMP was added to the perfusate at reperfusion (0.110 +/- 0.022 and 0.103 +/- 0.021, 0.123 +/- 0.029 and 0.164 +/- 0.024, and 0.153 +/- 0.030 and 0.170 +/- 0.027 ml.min-1.cmH2O-1.100 g-1, respectively). I-R significantly increased total, arterial, and venous vascular resistances. These increases in vascular resistance were also blocked by ISO, FSK, and DBcAMP. These data suggest that beta-adrenergic stimulation, post-beta-receptor activation of adenylate cyclase, and DBcAMP prevent the changes in pulmonary vascular permeability and vascular resistances caused by I-R in isolated rabbit lungs through a mechanism involving an increase in intracellular levels of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document