Endothelium-dependent effects of cigarette smoke components on tone of porcine intrapulmonary arteries in vitro.
The acute effects of cigarette smoking on the pulmonary vasculature are poorly understood--both vasodilatory and vasoconstrictive effects have been described. To investigate the mechanisms involved, strips of pig intrapulmonary arteries with and without intact endothelium were exposed to an extract of cigarette smoke made by bubbling smoke through phosphate-buffered saline. After contraction with norepinephrine (2.5 X 10(-7) M), smoke extract (concentration range 0.001 to 0.5%) caused a biphasic response in strips with intact endothelium--relaxation at lower concentrations and contraction at higher concentrations. Both relaxation and contraction responses were absent in strips without endothelium. Blockade of muscarinic, beta adrenergic, serotonergic, and histamine type 1 and 2 receptors did not alter the effects. Indomethacin (5 X 10(-6) M) or acetylsalicylic acid (10(-4) M) blocked the relaxation but not contraction effects of smoke extract, suggesting that relaxation was due to cyclooxygenase products of arachidonic acid. Nicotine caused endothelium-dependent contraction of intrapulmonary arteries and the contractile effects of both nicotine and smoke extract were blocked by hexamethonium (10(-6) M). However, the contractile effects of cigarette smoke components are more potent than those of nicotine. These findings help explain previously described acute effects of smoking on the pulmonary vasculature and provide insight into the mechanisms involved.
Holden
W E
WE
Department of Medicine, Portland VA Medical Center, Oregon.
Kishiyama
S S
SS
Dong
S P
SP
Osborne
M L
ML
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010947:Plants, Toxic; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D012906:Smoke / Q000009:adverse effects*; D013552:Swine; D014026:Nicotiana
D016861:Cyclooxygenase Inhibitors; D006584:Hexamethonium Compounds; D012906:Smoke; D009538:Nicotine; D001241:Aspirin; D009638:Norepinephrine; D007213:Indomethacin