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.

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.

Vascular reactivity and permeability to serotonin in cyclooxygenase-inhibited dog lung

1988 ◽  
Vol 255 (5) ◽  
pp. H1096-H1105
Author(s):  
W. F. Hofman ◽  
I. C. Ehrhart
Keyword(s):  
Vascular Reactivity ◽  
Pressor Response ◽  
Left Lung ◽  
Base Line ◽  
Fluid Filtration ◽  
Lung Lobe ◽  
Pressor Responses ◽  
Pulmonary Arterial ◽  
Group 5 ◽  
Dose Dependent Increase

We examined the effects of serotonin (5-HT) infusion on hemodynamics, vascular compliance (Cvasc), and the filtration coefficient (Kf) in the isolated canine lower left lung lobe (LLL) perfused at constant flow. In one group (5-HT; n = 8), 5-HT was infused at 55 micrograms/min for 35 min and then at 105 micrograms/min for 15 min before and during a Kf determination. Cyclooxygenase inhibition (COI) was induced by 40 microM indomethacin (n = 4) or 45 microM meclofenamate (n = 4) before 5-HT infusion in a second group (5-HTCOI; n = 8). Control LLLs (n = 8) were given equivalent volumes of saline. The pulmonary arterial pressure (Pa) increase to 55 micrograms/min 5-HT (3.0 +/- 0.6 Torr; 43.7%) was nearly doubled (P less than 0.01) with COI (10.5 +/- 1.5 Torr; 83.3%), while LLL weight decreased 6.2 g/100 g in both groups. With 5-HT infusion, the dose-dependent increase in Pa, lobar vascular resistance, and precapillary resistance was greater (P less than 0.05) in the 5-HTCOI than the 5-HT group, but capillary pressure (Pc) was not increased from base-line values. Kf values did not differ (P greater than 0.05) among groups but Cvasc was reduced (P less than 0.05) in the 5-HTCOI group. We found that 5-HT increases Pa, but does not appear to promote microvessel fluid filtration by increasing Pc or the Kf. The enhanced and sustained pressor response to 5-HT with COI suggests that vasodilatory prostaglandins may modulate pressor responses to 5-HT.

Effects of chronic hypoxia on pulmonary vascular responses to biogenic amines

1983 ◽  
Vol 55 (2) ◽  
pp. 534-540 ◽  
Author(s):  
R. J. Porcelli ◽  
M. J. Bergman
Keyword(s):  
Biogenic Amines ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Chronic Hypoxia ◽  
Receptor Activity ◽  
Vascular Responses ◽  
Vascular Contractility ◽  
Beta Receptor ◽  
Pressor Responses

The effects of chronic hypoxia on pulmonary vascular resistance changes (% delta Rpv) to histamine, 5-hydroxytryptamine (5-HT), norepinephrine (NE), and KCl were studied in isolated perfused lungs from control rats and rats exposed to 7, 14, and 28 days of hypoxia. Histamine, which produced linear increases in % delta Rpv with increasing doses in the control, was reversed to vasodilation by chronic hypoxia of 7 and 14 days and at 28 days, vasodilation to this amine still predominated (7 out of 10). Control responses to 5-HT were unaltered by 7 days of hypoxia but enhanced at 14 and 28 days. Control responses to NE showed either vasoconstriction or vasodilation; at 7 days of hypoxia, NE had no significant vasoactivity; however, at 14 days, vasoconstriction and vasodilation were both observed, with vasodilation being more effective. Lastly, the pressor responses to KCl were not affected by chronic hypoxia of any duration. These results suggest that chronic hypoxia: 1) does not alter pulmonary vascular contractility (KCl); 2) reduces H1 and alpha-receptor activity while enhancing H2- and beta-receptor activity; and 3) enhances the pressor responses to 5-HT by increasing either the efficacy of this amine or the number of 5-HT vasoconstrictor receptors.

Hyperglucagonemia and alpha-adrenergic receptor in acute hypoxia.

1979 ◽  
Vol 237 (5) ◽  
pp. E404 ◽  
Author(s):  
D Baum ◽  
D Porte ◽  
J Ensinck
Keyword(s):  
Oxygen Deficiency ◽  
Acute Hypoxia ◽  
Beta Blockade ◽  
Similar Degree ◽  
Adrenergic Blockade ◽  
Group Iii ◽  
Group I ◽  
Alpha Blockade ◽  
Group Ii ◽  
Hypoxic Group

The plasma immunoreactive glucagon (IRG) response to hypoxia was studied in puppies. Three groups of paired experiments were performed. In group I, 8% O2:92% N2 ventilation (PaO2 20--30 torr) produced a rise in plasma IRG and glucose as well as hypotension and bradycardia. However, when group I was air ventilated (PaO2 greater than 70 torr) and given glucose infusions producing hyperglycemia of similar degree, plasma IRG was unchanged. Group II received alpha-adrenergic blockade (phenoxybenzamine). When made hypoxic, group II developed no significant IRG rise and less hyperglycemia than with hypoxia alone. Hypotension was more severe with hypoxia plus alpha-blockade. Phenoxybenzamine itself did not change plasma IRG or glucose during air breathing. Group III receivi developed hyperglucagonemia and hyperglycemia not significantly different from that with hypoxia alone. However, hypoxia-caused hypotension and bradycardia was more pronounced with beta-blockade. No change in plasma IRG or glucose occurred in group III animals breathing air. These data suggest that a) glucagon release is caused by acute oxygen deficiency, and b) the hypoxic response is largely adrenergically mediated with the major role played by the alpha-receptor.

Pulmonary vascular reactivity after repetitive exposure to selected biogenic amines

1983 ◽  
Vol 55 (6) ◽  
pp. 1868-1876 ◽  
Author(s):  
M. Cutaia ◽  
R. J. Porcelli
Keyword(s):  
Biogenic Amines ◽  
Dose Response ◽  
Vascular Reactivity ◽  
Lower Lobe ◽  
Left Lower Lobe ◽  
Base Line ◽  
Response Curves ◽  
Arterial Blood ◽  
Repetitive Exposure ◽  
Dose Response Curves

The present study investigated the effects of repetitive exposure to a select group of biogenic amines (epinephrine, norepinephrine, histamine, and serotonin) on pulmonary vascular reactivity by constructing and analyzing a set of four sequential cumulative dose-response curves to one biogenic amine in the isolated blood-perfused left lower lobe of the cat lung in vivo. The dose-response curves were obtained under conditions of constant flow, insuring that the observed pressure changes in the lobe were pressor responses resulting from vasoconstriction rather than flow-related changes. Histamine and epinephrine demonstrated a progressive loss of initial vasoconstrictor activity, whereas the responses to serotonin remained unchanged after repetitive exposure. Norepinephrine demonstrated two different patterns of response, depending on the dose range employed; norepinephrine (0.068-2.27 nmol/ml) demonstrated a loss of the original vasoconstrictor activity, in a pattern similar to histamine and epinephrine, while higher doses of norepinephrine (0.34-9.1 nmol/ml) demonstrated no change in activity with a left shift in the concentration at which the maximal responses occurred, suggesting an increase in sensitivity as a result of repeated exposure. These results were obtained in the absence of significant alterations of arterial blood gases, changes in base-line tone in the experimental left lower lobe, or the development of severe pulmonary edema. These data suggest that only the agents that are capable of stimulating antagonistic vasoconstrictor and vasodilator receptors demonstrated a loss of pulmonary vasoconstrictor activity, which may result from a functional shift in the balance of antagonistic receptor activity with continued exposure.

Regulation of blood pressure in pregnancy: pressor system blockade and stimulation

1990 ◽  
Vol 258 (5) ◽  
pp. H1559-H1572 ◽  
Author(s):  
Z. R. Pan ◽  
M. D. Lindheimer ◽  
J. Bailin ◽  
W. M. Barron
Keyword(s):  
Vascular Reactivity ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Pressor Responses ◽  
Before And After ◽  
Alpha Blockade ◽  
Near Term ◽  
Regulation Of Blood Pressure ◽  
In Pregnancy

Contributions of the autonomic nervous system (ANS), renin-angiotensin system (RAS), and arginine vasopressin (AVP) to basal mean arterial pressure (MAP) were evaluated in near-term pregnant and virgin rats as follows. MAP and heart rate (HR) were measured before and after ganglionic, alpha-adrenoreceptor, RAS, and/or AVP blockade. In addition, pressor responses to angiotensin II (ANG II), norepinephrine, phenylephrine, or AVP were determined in ganglionic-blocked animals. In both groups decrements in MAP were greatest after ganglionic or alpha-blockade, intermediate after RAS blockade, and negligible after AVP-V1 antagonism ([d(CH2)5Tyr(Me)]AVP). Recovery of MAP was also similar in the two groups except after phentolamine when MAP and HR remained lower in gravid rats. Superimposition of RAS or AVP blockade during phentolamine infusion suggested that ANG II and AVP were less effective in supporting MAP during alpha-blockade in pregnancy. Pressor responses to ANG II and norepinephrine during ganglionic blockade were markedly blunted during pregnancy; however, those to phenylephrine and AVP were unchanged. We conclude that contributions of ANS, RAS, and AVP to basal MAP are similar in pregnant and virgin rats; neural mechanisms dominating in both groups. However, recovery during alpha-blockade is impaired during gestation, apparently due to blunted HR responses and decreased pressor contributions of ANG II and AVP. This may be explained, in part, by decreased vascular reactivity to ANG II, although a similar mechanism cannot be invoked for AVP.

Age-dependent effects of chronic hypoxia on pulmonary vascular reactivity

1987 ◽  
Vol 63 (3) ◽  
pp. 1122-1129 ◽  
Author(s):  
M. A. Lowen ◽  
M. J. Bergman ◽  
M. V. Cutaia ◽  
R. J. Porcelli
Keyword(s):  
Vascular Reactivity ◽  
Chronic Hypoxia ◽  
Hypoxic Exposure ◽  
Base Line ◽  
Adult Rats ◽  
Mature Adult ◽  
Important Interaction ◽  
Pressor Responses ◽  
Old Adult ◽  
Series Of Experiments

Effects of age on the pulmonary vascular responses to histamine (HIST), norepinephrine (NE), 5-hydroxytryptamine (5-HT), and KCl were studied in isolated, perfused lungs from juvenile (7-wk-old), adult (14-wk-old), and mature adult (28-wk-old) normoxic rats and compared with age-matched rats exposed to chronic hypoxia for either 14 or 28 days. Chronic hypoxia changed vasoconstriction to HIST and NE to vasodilation in lungs from juvenile and adult rats. Mature adult lungs only vasoconstricted to these amines in both control and hypoxic animals. Pressor responses to 5-HT were not affected by chronic hypoxia regardless of age group. Pressor responses to KCl were also not altered by hypoxia, but lungs from older rats showed greater control responsiveness to KCl compared with lungs from juveniles. Only lungs from juvenile animals developed significant elevations of base-line resistance as a result of hypoxic exposure. To investigate the contribution of H1-, H2-, and beta-receptors in these changes, we employed chlorpheniramine, metiamide, and propranolol, respectively, as blocking agents in another series of experiments. Chlorpheniramine either reduced vasoconstriction or increased vasodilation to HIST in lungs from both control and hypoxic animals, whereas metiamide was without effect. Propranolol either increased vasoconstriction or reversed vasodilation to HIST and NE in all lungs studied. The present data demonstrate the important interaction between chronic hypoxia and age that can alter pulmonary vascular tone and reactivity. The inverse relationship between age and elevation of pulmonary vascular resistance after chronic hypoxic exposure may be the key element that changes pulmonary vascular reactivity observed during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

Endothelial injury and vascular reactivity in monocrotaline pulmonary hypertension

1988 ◽  
Vol 255 (6) ◽  
pp. H1484-H1491 ◽  
Author(s):  
H. C. Rosenberg ◽  
M. Rabinovitch
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Light Microscopy ◽  
Vascular Reactivity ◽  
Acute Hypoxia ◽  
Pulmonary Arteries ◽  
Significant Rise ◽  
Endothelial Injury ◽  
Base Line ◽  
Sprague Dawley

We used awake, unsedated rats with indwelling cardiovascular catheters to study the role of endothelial injury and increased pulmonary vascular reactivity in the pathogenesis of monocrotaline (MC)-induced pulmonary hypertension. Hemodynamic findings were correlated with morphometric analyses of alterations in the vascular endothelium assessed by electron microscopy and of muscularization of pulmonary arteries assessed by light microscopy. Male Sprague-Dawley rats (200–250 g) were injected with MC (60 mg/kg) or with saline vehicle. The hemodynamic response to acute hypoxia (10% O2 for 10 min) was studied at 4, 8, and 12 days postinjection. Pulmonary artery pressures and resistances (Ppa, Rp) were similar in saline- and MC-injected rats at 4 and 8 days postinjection. In response to acute hypoxia, the rise in Ppa was also similar, but there was a slight but significant rise in Rp, (P less than 0.05) in the 8-day group, due largely to a decrease in cardiac output. At 12 days after injection, base-line Ppa was increased in MC-injected rats (P less than 0.01) and there was a heightened response to hypoxia assessed both as a significant increase in Ppa and Rp (P less than 0.05 each). Endothelial injury was observed as early as 4 days postinjection with pallor and swelling evident qualitatively and by a decreased proportion of microfilaments (P less than 0.05) assessed quantitatively. By light microscopy, extension of smooth muscle into normally nonmuscularized pulmonary arteries was evident by 8 days postinjection. By 12 days postinjection there was marked extension of smooth muscle present (P less than 0.01) with medial hypertrophy of muscular arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

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