Pulmonary vascular effects of prostaglandin D2, but not its systemic vascular or airway effects, are mediated through thromboxane receptor activation

Landon Stuart King, M. Fukushima, M. Banerjee, K. H. Kang, J. H. Newman, I. Biaggioni

Research output: Contribution to journalArticle

Abstract

Prostaglandin D2 (PGD2) can cause pulmonary vasoconstriction or vasodilation depending on animal species and age. Because the constrictor effects of PGD2 in some vascular beds may be mediated through thromboxane receptors, the purpose of this study was to determine whether the vascular or bronchial effects of PGD2 are mediated through thromboxane/endoperoxide (TX/E) receptor activation. In chronically instrumented awake sheep, PGD2 (5-25 μg/kg i.v.) produced a dose-dependent increase in pulmonary arterial pressure and in systemic arterial blood pressure. These changes were due to increases in resistance, because cardiac output remained unchanged. PGD2 also decreased dynamic compliance at lower doses (0.1-5 μg/kg i.v.) than those required to produce pulmonary vasoconstriction, confirming that PGD2 is a potent bronchoconstrictor. The airway and systemic vascular effects of PGD2 were not altered by TX/E receptor antagonism. In contrast, PGD2-induced pulmonary vasoconstriction was blocked by two TX/E receptor antagonists, SQ-29,548 and AH-23848, implying that this effect is mediated through activation of TX/E receptors. The pulmonary vasoconstrictor effects of PGD2 could not be explained by thromboxane generation, because neither cyclooxygenase inhibition with ibuprofen nor thromboxane synthase inhibition with OKY-046 had any effect on PGD2 actions. In contrast, a mild but consistent pulmonary vasodilation produced by PGD2 could be uncovered if the pulmonary vascular bed was preconstricted by hypoxia with simultaneous TX/E receptor blockade. These results indicate that TX/E receptor antagonists, although still useful pharmacological probes to determine the role of TX/E receptor activation in pathophysiological processes, should not be used to infer a role of endogenous thromboxane A2. It is possible that PGD2 participates in pulmonary processes previously ascribed uniquely to thromboxane A2.

Original languageEnglish (US)
Pages (from-to)352-358
Number of pages7
JournalCirculation Research
Volume68
Issue number2
StatePublished - 1991
Externally publishedYes

Fingerprint

Thromboxane Receptors
Prostaglandin D2
Blood Vessels
Lung
Vasoconstriction
Thromboxane A2
Thromboxanes
Vasodilation
Arterial Pressure
Bronchoconstrictor Agents
Ibuprofen
Vasoconstrictor Agents
Prostaglandin-Endoperoxide Synthases
Cardiac Output
Compliance

Keywords

  • bronchial spasm
  • Prostaglandin D
  • prostaglandin F
  • pulmonary circulation
  • sheep
  • thromboxane A

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Pulmonary vascular effects of prostaglandin D2, but not its systemic vascular or airway effects, are mediated through thromboxane receptor activation. / King, Landon Stuart; Fukushima, M.; Banerjee, M.; Kang, K. H.; Newman, J. H.; Biaggioni, I.

In: Circulation Research, Vol. 68, No. 2, 1991, p. 352-358.

Research output: Contribution to journalArticle

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