Cigarette smoke extract potentiates bradykinin-induced increases in microvascular permeability.
The first goal of this study was to determine whether cigarette smoke extract (CSE) increases microvascular permeability of the hamster cheek pouch in vivo. The second goal was to determine whether CSE potentiates bradykinin-induced increases in vascular permeability in the hamster cheek pouch. Using intravital microscopy, we examined the permeability of the hamster cheek pouch to fluorescein isothiocyanate-dextran (mol wt 70,000). Increases in permeability were quantitated by counting the number of postcapillary venular leaky sites per 0.11 cm2. Superfusion of CSE (1, 5, and 10%) did not produce venular leaky sites and, thus, did not alter macromolecular permeability. Superfusion of bradykinin (0.1, 0.5, and 1.0 microM) produced a dose-related increase in the number of venular leaky sites. Formation of leaky sites in response to bradykinin was potentiated by CSE. To determine whether potentiation of bradykinin-induced leaky site formation by CSE was related to products released via the cyclooxygenase pathway, we examined the effects of pretreatment with indomethacin (10 mg/kg i.v.). Indomethacin did not alter the potentiating effect of CSE on bradykinin-induced leaky site formation. These findings suggest that CSE does not alter basal permeability of the hamster cheek pouch microcirculation in vivo. However, CSE potentiates bradykinin-induced increases in microvascular permeability. The mechanism of CSE-induced potentiation of microvascular permeability does not appear to be related to substances produced via the cyclooxygenase pathway.
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575.
Rubinstein
I
I
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D009061:Mouth Mucosa / Q000098:blood supply; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D012907:Smoking / Q000503:physiopathology*
D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases; D016650:Fluorescein-5-isothiocyanate; D001920:Bradykinin; D007213:Indomethacin