Platelet-activating factor antagonists increase vascular reactivity in perfused rat lungs.
Platelet-activating factor (PAF) administered to the pulmonary circulation in low dose (nanogram) has vasodilatory properties. Therefore, we investigated whether endogenous PAF plays a role in the control of tone in the pulmonary circulation. The PAF receptor antagonists, SRI 63-441 (2.6 X 10(-4) M) and L659,989 (1 X 10(-5) M), were the major investigative tools. In isolated perfused rat lungs, both agents caused a persistent increase in base-line perfusion pressure (Ppa), potentiated angiotensin II (ANG II) vasoconstriction, and potentiated hypoxic vasoconstriction (HPV). This potentiation of ANG II and HPV was found to be independent of circulating blood elements. Vasodilation in the presence of PAF blockade was also impaired. The combination of cyclooxygenase inhibition and PAF receptor blockade had an additive effect on ANG II vasoconstriction but did not cause more potentiation of HPV than achieved with PAF antagonism alone. In vivo, SRI 63-441 (10 mg/kg) caused only a transient increase in base-line Ppa without altering ANG II and hypoxic vasoconstriction. These findings support a vasodilatory role for endogenous PAF in the pulmonary circulation.
Haynes
J
J
Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver 80262.
Chang
S W
SW
Morris
K G
KG
Voelkel
N F
NF
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D005663:Furans / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011806:Quinolinium Compounds / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects
D005663:Furans; D010972:Platelet Activating Factor; D011806:Quinolinium Compounds; C050531:SRI 63-441; D000804:Angiotensin II; C054893:L 659989