The possible role of prostaglandin D2 in the long-lasting airways vasodilatation induced by allergen in the sensitized pig.
Allergen-induced nasal and bronchial vasodilatation and bronchoconstriction were studied in ascaris-sensitized pigs with and without pretreatment with diclofenac sodium, to evaluate the contribution of prostanoids in these responses. The bronchoconstriction induced by allergen aerosol challenge was enhanced by diclofenac, whereas the duration of the bronchial vasodilatation was reduced from 80 to 30 min, without changing the maximal effect. However, both the maximal effect and the duration of the nasal vasodilatation were reduced upon nasal allergen challenge by 60% (P less than 0.01) and from 72 to 16 min (P less than 0.05), respectively. Bronchial challenge with the allergen also induced nasal vasodilatation of long duration and this response was highly sensitive to diclofenac pretreatment. I.v. injections of prostaglandins (PG) E1, E2, I2 and D2 revealed that only PGD2 induced vasodilatation of long duration in the airways without major effects on the systemic arterial blood pressure. Nebulization of PGD2 (0.7-1.4 mumol) into the pig airways also induced marked vasodilatation of long duration (greater than or equal to 40 min), especially in the nasal circulation. The vasodilatory responses to PGD2 were not changed by systemic pretreatment with capsaicin or diclofenac. Challenge in the airways with platelet-activating factor (PAF) produced bronchial and vascular responses similar to those seen with the allergen and the vasodilatory responses to PAF were partly sensitive to diclofenac. We propose that a long-lasting component of the allergen-induced vasodilatation in the pig airways, especially in the nasal mucosa, may be caused by the release of PGD2, acting independently of sensory nerves. Allergen and PAF aerosol challenge in the lung may also induce the release of a vasodilatory prostaglandin, possibly PGD2 into the systemic circulation, thereby inducing nasal vasodilatation.
Alving
K
K
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Matran
R
R
Lundberg
J M
JM
D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001200:Ascaris / Q000276:immunology; D001980:Bronchi / Q000098:blood supply / Q000187:drug effects / Q000276:immunology; D004008:Diclofenac / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000494:pharmacology / Q000502:physiology*; D011453:Prostaglandins / Q000494:pharmacology; D012137:Respiratory System / Q000098:blood supply* / Q000187:drug effects / Q000276:immunology; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000485:Allergens; D010972:Platelet Activating Factor; D011453:Prostaglandins; D004008:Diclofenac; D015230:Prostaglandin D2