Cigarette smoke extract attenuates endothelium-dependent arteriolar dilatation in vivo

Abstract

The purpose of this study was to examine the effects of cigarette smoke extract on endothelium-dependent and endothelium-independent dilatation of arterioles in vivo. Using intravital microscopy, we measured diameter of arterioles contained within the microcirculation of the hamster cheek pouch during suffusion with acetylcholine and nitroglycerin, before and after treatment with cigarette smoke extract. Under control conditions, acetylcholine and nitroglycerin produced dose-related dilatation of cheek pouch arterioles. Superfusion of cigarette smoke extract (1.0%) did not alter baseline diameter of arterioles or vasodilatation in response to nitroglycerin but impaired dilatation of arterioles in response to acetylcholine. Next, we examined the possibility that impaired dilatation of cheek pouch arterioles in response to acetylcholine after exposure to cigarette smoke extract may be related to the release of substances produced via the cyclooxygenase pathway. In indomethacin-pretreated hamsters, acetylcholine produced similar vasodilatation before and after exposure to cigarette smoke extract. Thus these findings suggest that cigarette smoke extract impairs endothelium-dependent responses of cheek pouch arterioles. The mechanism of impaired responses of cheek pouch arterioles after exposure to cigarette smoke extract appears to be related to the release of substances produced via the cyclooxygenase pathway.

Mechanisms MediatingPorphyromonas gingivalisGingipain RgpA-Induced Oral Mucosa Inflammation In Vivo

“…These data suggest that at low concentrations gingipain RgpA stimulates the production of anti-inflammatory prostaglandins in the cheek pouch that partly counteract the edema-forming effects of the proteinase (23,25). However, at high concentrations of gingipain RgpA the salutary effects of these compounds are circumvented, in part, by local elaboration of bradykinin.…”

“…This observation implies that the edema-forming effects of gingipain RgpA are catalytic site dependent. Lastly, indomethacin, at a concentration that inhibits cyclooxygenase in the cheek pouch (23,25), amplified macromolecular efflux elicited by a low (submaximal) concentration of gingipain Saline ( a Values are means Ϯ standard errors of the means; for each group, n ϭ 4 animals. GRgpA, gingipain RgpA; PI mixture, mixture of proteinase inhibitors consisting of aprotinin (5 g/ml), soybean trypsin inhibitor (100 g/ml), bestatin (10 M), and DL-2-mercapto-methyl-3-guanidinoethylthiopropanoic acid (10 M).…”

“…The concentrations of gingipain RgpA, NPC 17647, leupeptin, and indomethacin used in these experiments were based on previous studies in our laboratory and reports in the literature (2,3,7,14,15,23,25,26,28,33). The concentration of indomethacin used has been shown to inhibit cyclooxygenase in the cheek pouch (23,25). The composition of the mixture of proteinase inhibitors and the concentrations of its constituents used in these studies were based on previous stud-ies in our laboratory and reports in the literature (3,7,17,20,22,29).…”

Subtilisin Increases Macromolecular Efflux from the Oral Mucosa

“…In preliminary studies, I determined that infusion of indomethacin (10 mg/kg) alone for 30 min was associated with no visible leaky site formation or increase in clearance of FITC-dextran (data not shown). The concentration of indomethacin used in these studies was based on a previous study in my laboratory and has been previously shown to inhibit cyclooxygenase in the cheek pouch (24,27). .…”

Nitric oxide synthase–dependent responses of the basilar artery during acute infusion of nicotine

“…Active and passive exposure to cigarette smoke impairs NOSdependent reactivity of large and small peripheral vessels in animals ( Mays et al, 1999 ;Murohara, Kugiyama, Ohgushi, Sugiyama, & Yasue, 1994 ;Rubinstein, Yong, Rennard, & Mayhan, 1991 ) and humans ( Celermajer et al, 1996 ;Sumida et al, 1998 ). The cellular mechanism that contributes to impaired vascular function during exposure to cigarette smoke appears to involve oxygen-derived free radicals (Mays et al, 1999 ;Murohara et al, 1994 ;Ota et al, 1997 ).…”