Augmented myocardial ischaemia by nicotine--mechanisms and their possible significance.
1. To study the effect of nicotine on the severity of experimental myocardial ischaemia, Langendorff hearts of rabbits (n=7-12 per group) were subjected to 2 h of low-flow ischaemia followed by 1 h of reperfusion. 2. Infusion of nicotine (100 ng ml(-1)) caused only minor changes in non-ischaemic conditions but a significant (P<0.05) increase in end-diastolic pressure (LVEDP), loss of creatine kinase (CK) and troponin (TnT) as well as increase in noradrenaline (NA) overflow in reperfused ischaemic hearts. 3. RT PCR was done on total RNA for mRNA expression of the constitutive (COX-1) and inducible cyclooxygenase (COX-2). There was no COX-2 in non-ischaemic hearts but a significant expression in ischaemia (n=5) which was further increased by nicotine. These data were confirmed at the protein level by Western blotting and additionally shown that COX-1 remained unchanged. 4. There was a marked increase in prostacyclin (PGI2) and a 2 fold increase in NA overflow which were both stimulated by nicotine. 5. The aggravating effects of nicotine on myocardial ischaemia (CK release) as well as the expression of COX-2 mRNA were prevented by pretreatment with the beta-blocker pindolol (1 microM). 6. The data demonstrate marked deleterious actions of nicotine in reperfused ischaemic hearts. These actions are probably related to the increase in catecholamine overflow, are beta-receptor-mediated and involve enhanced gene expression of COX-2.
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany.
K
K
Schrör
K C
KC
Zimmermann
R
R
Tannhäuser
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers; D002395:Catecholamines / Q000378:metabolism; D051546:Cyclooxygenase 2; D011464:Epoprostenol / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000201:enzymology* / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010869:Pindolol / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D002395:Catecholamines; D007527:Isoenzymes; D012333:RNA, Messenger; D009538:Nicotine; D010869:Pindolol; D011464:Epoprostenol; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D009638:Norepinephrine