title: Paradoxically enhanced bradykinin-induced venodilation in young, healthy, short-term smokers.
abstract: Bradykinin is a nonapeptide, whose mechanism of vasodilation is mediated chiefly through the release of endothelium-derived relaxing factor (EDRF). Diminished vasodilatory response to EDRF has been demonstrated in many pathologic states such as hypertension, atherosclerosis, diabetes, and long-term, heavy smoking. We studied whether the diminished EDRF-mediated vasodilatory response seen in chronic diseases can be demonstrated in young, clinically healthy smokers. We used the dorsal hand-vein compliance technique, an in vivo technique used to measure response to local infusions of vasoactive substances. Full dose-response curves to bradykinin (dosing range, 0.5-500 ng/min) were generated in 11 young, healthy smokers and 11 young, healthy nonsmokers by using hand veins preconstricted with phenylephrine (dosing range, 20-6,800 ng/min). In addition, after a washout period, a single maximal dose of a non-endothelium-dependent vasodilator, isoproterenol (300 ng/min) was infused. Our results demonstrated that smokers had a greater maximal venodilation to bradykinin than did nonsmokers (106 +/- 40% vs. 69 +/- 49%; p < 0.05). The log of the dose that produced half-maximal response to bradykinin was smaller in smokers: -0.10 +/- 0.93 (0.79 ng/min) versus 0.75 +/- 0.84 (5.6 ng/min); p < 0.05. There was no difference in the maximal dilatory response to isoproterenol: 80 +/- 45% (smokers) versus 89 +/- 50% (nonsmokers), nor was there a difference in the log dose of phenylephrine necessary to produce 80% constriction of the hand vein (2.7 +/-0.7 vs. 2.7 +/- 0.9 ng/min) between the two groups. We conclude that young, otherwise healthy smokers have a paradoxic hyperactive response to the endothelium-dependent vasodilator, bradykinin, but maintain a similar response to the nonendothelium-dependent vasodilator, isoproterenol as compared with nonsmokers. Their reactivity to the alpha1-adrenergic agonist phenylephrine was found to be intact. It is possible that a hyperactive response to EDRF in young smokers contributes to endothelium damage seen in chronic disease. To our knowledge, this is the first report on increased reactivity to bradykinin in short-term smokers.
authors.affiliation: Department of Medicine, Maricopa Medical Center, Phoenix, Arizona, USA. zvajo@usa.net
authors.forename: Z
authors.initials: Z
authors.lastname: Vajo
authors.forename: B
authors.initials: B
authors.lastname: Szekacs
authors.forename: M H
authors.initials: MH
authors.lastname: McDonald
authors.forename: B
authors.initials: B
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Srivathsan
authors.forename: W D
authors.initials: WD
authors.lastname: Dachman
mesh_terms: D000328:Adult; D001920:Bradykinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D012907:Smoking / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D009569:Nitric Oxide; D001920:Bradykinin