title: Cardiac necrosis markers associated with low nitric oxide levels in the plasma of rabbits after treatment with vasopressin: protective effects of nitroglycerin administration.
abstract: It has been reported that the administration of vasopressin induces myocardial ischaemia in rats, which causes electrocardiographic ST segment alterations according to many authors. But rat electrocardiogram (ECG) lacks ST segment. Consequently it appears important to study the effects of vasopressin in rabbits, which show ST segment present in the ECG. Since cardiac necrosis markers are released in the plasma of humans with myocardial infarction, as well as in a variety of experimental models of myocardial necrosis, it is possible that the same may occur in rabbits with myocardial ischaemia induced by vasopressin. The main aim of this study was to investigate whether the administration of vasopressin causes the appearance of specific myocardial necrosis markers, such as cardiac troponin I, myoglobin or creatine kinase MB (CK MB) in rabbits in the presence or absence of modified ECG profile, and to also verify whether these markers are associated with the alterations in some coagulation parameters, that are known to be induced by vasopressin. As the effects of vasopressin are counteracted by nitric oxide (NO), another aim was to verify whether vasopressin also affects plasma NO levels and whether the administration of a NO donor can reverse these effects. Vasopressin was administered to rabbits and caused ischaemic alterations such as electrocardiographic changes, and significantly increased the levels of plasma cardiac necrosis markers (c-troponin I, myoglobin and CK MB). It also elevated diastolic blood pressure (BP), lowered heart rate (HR), increased procoagulation activity, and lowered plasma NO levels. The appearance of heart necrosis, demonstrated by plasma cardiac necrosis markers in the animals receiving vasopressin, was attributed to a drug-induced increase in vasoconstriction and coagulation activity. The intense vasoconstriction and thrombosis may lead to endothelium necrosis and a consequent drop in NO production. The administration of the NO donor nitroglycerin (NG) in the vasopressin treated animals restored NO values, and was capable of preventing the appearance of the plasma cardiac necrosis markers and altered coagulation values. The protective activity of NG was attributed to NO release, which lowers BP values and counteracts coagulation activity in vasopressin-treated animals. The described procedure may also be proposed for the study of early ischaemic myocardial lesions and the screening of NO donors preventing myocardial damage.
authors.affiliation: Institute of Pathology, Department of Pharmacology, Ospedale Niguarda Ca' Granda, Via Vanvitelli 32, 20129 Milan, Italy. arnaldo.pinelli@unimi.it
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Pinelli
authors.forename: Silvio
authors.initials: S
authors.lastname: Trivulzio
authors.forename: Livio
authors.initials: L
authors.lastname: Tomasoni
authors.forename: Boris
authors.initials: B
authors.lastname: Bertolini
authors.forename: Sergio
authors.initials: S
authors.lastname: Brenna
authors.forename: Edgardo
authors.initials: E
authors.lastname: Bonacina
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D052279:Creatine Kinase, MB Form; D004562:Electrocardiography / Q000187:drug effects; D005340:Fibrinogen / Q000032:analysis; D007527:Isoenzymes / Q000097:blood; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009211:Myoglobin / Q000097:blood; D009336:Necrosis; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology*; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011817:Rabbits; D019210:Troponin I / Q000097:blood; D014667:Vasopressins / Q000008:administration & dosage*
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D009211:Myoglobin; D020030:Nitric Oxide Donors; D019210:Troponin I; D014667:Vasopressins; D009569:Nitric Oxide; D005340:Fibrinogen; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form; D005996:Nitroglycerin