Effects of Temperature Changes on the Pressor Response to Acute Alveolar Hypoxia in Isolated Rat Lungs

Nilsen, Katrine; Hauge, Anton

doi:10.1111/j.1748-1716.1968.tb04088.x

Cited by 21 publications

(3 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…"- 3 4 Inhibition of hypoxic pressor responses by relatively high levels of these agents might be related to calcium antagonism or hyperpolarization rather than to a-adrenergic blockade, 36 histamine antagonism," and histamine depletion. 36 Similarly, inhibition of hypoxic vasoconstriction in intact dogs by increased plasma levels of MgCl 2 37 and in isolated lungs by decreased perfusate temperature 38 possibly is related, in the first case, to calcium antagonism by magnesium"'" and, in the latter, to a decrease in membrane permeability to calcium induced by cooling. 19 In summary, a critical dependence of the hypoxic mechanism for pulmonary vasoconstriction on membrane depolarization and transmembrane calcium influx would explain inhibition of this response by agents that hyperpolarize the plasma membrane or reduce membrane permeability to calcium.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs.

McMurtry¹,

Davidson²,

Reeves³

et al. 1976

Circulation Research

350

147

View full text Add to dashboard Cite

SUMMARY The role of a transmembrane calcium influx in hypoxic pulmonary vasoconstriction was studied in isolated, bloodperfused, rat lungs. We reasoned that, if the influx of extracellular calcium mediated the hypoxic mechanism, pressor responses to alveolar hypoxia (2.5% O 3 ) would be susceptible to inhibition by the calcium antagonists verapamil (2 x 10 5 to 2 x 10 ' HIM) and SKF 525 A (2.6 to 260 IDM). Susceptibility of hypoxic pressor responses to inhibition by these calcium antagonists was contrasted to that of pressor responses elicited by the humoral vasoconstrictors angiotensin II (1 or 0.5 fig) and prostaglandin F to (10 jig). Since neither saralasin (0.5 JJM), a competitive antagonist of angiotensin II, nor meclofenamate (6.8 HM), an inhibitor of prostaglandin synthesis, depressed hypoxic pressor responses, it was concluded that these humoral transmitters were not directly involved in the hypoxic mechanism, and therefore served as independent reference agonists. The order of susceptibility of pulmonary pressor responses to inhibition by verapamil was hypoxia > angiotensin II > prostaglandin F^. SKF 525A also reduced pressor responses to hypoxia more readily than those to angiotensin II. The greater inhibition of hypoxic pulmonary vasoconstriction by both calcium antagonists suggested that the hypoxic mechanism was critically dependent on the transmembrane influx of extracellular calcium. Mediation of the hypoxic response by this type of excitation-contraction coupling is consistent with the idea that hypoxia has a direct depolarizing effect on the vascular smooth muscle. It also provides a unifying explanation for inhibition of the hypoxic mechanism by various agents that have depressant or stabilizing actions on membranes in addition to other pharmacological effects.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs.

McMurtry¹,

Davidson²,

Reeves³

et al. 1976

Circulation Research

350

147

View full text Add to dashboard Cite

show abstract

“…40 In general, the more prolonged and elaborate the manipulations before hypoxic testing, the more apt is the pulmonary circulation to show a high threshold for stimulation and a blunted vasoconstrictor response. These concerns are perennial among investigators on the pulmonary circulation and attempts have been made to take them into account in many different ways.…”

Section: Vasoactive Constituents In the Pulmonary Perfusatementioning

confidence: 99%

Hypoxia on the pulmonary circulation. How and where it acts.

Fishman¹

1976

Circulation Research

437

156

View full text Add to dashboard Cite

THIRTY YEARS have elapsed since von Euler and Liljestrand 1 advanced the proposition that acute hypoxia elicits pulmonary vasoconstriction. The idea was not new, 2 ' 8 but the report excited considerable interest because it was both propitious and prescient. Nineteen forty-six was a good year to perceive that the pulmonary vasoconstrictor response to hypoxia is part of a self-regulatory mechanism by which pulmonary capillary blood flow is automatically adjusted to alveolar ventilation: methods had been standardized for exploring the pulmonary circulation in a systematic and sophisticated way and the introduction of cardiac catheterization had brought the previously remote pulmonary circulation within reach.Much has been learned since then about the pulmonary circulation and the pressor response to acute hypoxia. Particularly helpful in dispelling the original misgivings about the occurrence of a pressor response to acute hypoxia has been a succession of observations on cattle in which the pulmonary pressor response to hypoxia is much greater than in the conventional laboratory animal, particularly in the postnatal period." That pulmonary vasoconstriction underlies the rise in pulmonary arterial pressure no longer is in doubt. 8 -8 The biological significance of this mechanism has been sought both in human disease 10 and in animals."' 13 And, the lessons from acute hypoxia have been extended to the chronic hypoxia of high altitude which also has proved to be associated with pulmonary vasoconstriction. 14 ' 15 As uncertainty after uncertainty evaporated, two key questions came into sharp focus: (1) By what mechanism(s) does hypoxia elicit vasoconstriction? (2) What segment(s) of the pulmonary vascular tree constrict(s) during hypoxia? The purpose of this paper is to offer a personal view of the answers to these questions. And, after having proposed how and where acute hypoxia works, brief consideration will be given to the question of how the observations on acute hypoxia-generally an artifice of the laboratory-are related to the state of chronic hypoxia which characterizes life at high altitude.

show abstract

“…Differences in hydrogen ion concentration (10,11), temperature (12), vascular tone (13), and thickness of pulmonary vascular smooth muscle (14) may all contribute to this variability. Controlling for all of these factors reduces but does not abolish the variability.…”

Section: Discussionmentioning

confidence: 99%

Variability of Hypoxic Pulmonary Vasoconstriction in Sheep

Ahmed

Oliver

Wanner³

1983

Am Rev Respir Dis

View full text Add to dashboard Cite

In a minority of conscious sheep, the hypoxic pulmonary vasoconstrictor response is blunted ("nonresponders"). The purpose of this investigation was to determine if this blunted response is related to an increased activity of H2-histamine receptors, beta-adrenergic receptors, or the generation of inhibitory prostaglandins. We measured pulmonary arterial pressure, pulmonary arterial wedge pressure, and pulmonary blood flow for the calculation of pulmonary vascular resistance (PVR) in 5 "nonresponders" and 5 sheep with a typical hypoxic pulmonary vasoconstrictor response ("responders") while breathing room air and 13% O2 (balance, N2). Arterial oxygen tension (PaO2) was also determined as a measure of the severity of hypoxia. During hypoxia, mean PVR increased by 6% (p = NS) in the "nonresponders" (PaO2, 49 +/- 4 mmHg), and by 70% (p less than 0.01) in the "responders" (mean PaO2, 46 +/- 4 mmHg). Metiamide (H2-blocker) and propranolol (beta-adrenergic blocker) pretreatments did not restore the hypoxic pulmonary vascular response in the "nonresponders," whereas pretreatment with indomethacin (prostaglandin synthetase inhibitor) caused mean PVR to increase by 48% (p less than 0.01) during hypoxia, indicating a partial restoration of hypoxic pulmonary vasoconstriction. In the "responders," the hypoxic pulmonary vascular response was not potentiated by indomethacin pretreatment (68% increase in mean PVR). We conclude that some sheep exhibit a blunted hypoxic pulmonary vasoconstrictor response caused by enhanced production of inhibitory prostaglandins.

show abstract

Effects of Temperature Changes on the Pressor Response to Acute Alveolar Hypoxia in Isolated Rat Lungs

Cited by 21 publications

References 14 publications

Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs.

Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs.

Hypoxia on the pulmonary circulation. How and where it acts.

Variability of Hypoxic Pulmonary Vasoconstriction in Sheep

Contact Info

Product

Resources

About