Drugs modifying nitric oxide metabolism affect plasma cholesterol levels, coagulation parameters, blood pressure values and the appearance of plasma myocardial necrosis markers in rabbits: opposite effects of L-NAME and nitroglycerine.
Various experiments have shown that decreased nitric oxide values alter plasma lipid levels or coagulation parameters or blood pressure values or cause myocardial necrosis phenomena, but it is not clear whether these alterations are reciprocally connected, or whether nitric oxide changes are involved in the appearance of some coronary disease risk factors (lipid, coagulation, blood pressure alterations) and myocardial necrosis.


OBJECTIVE
We modified nitric oxide levels in rabbits using L-NAME (a NO synthase blocker) or nitroglycerine (a NO donor), and simultaneously evaluated variations in total and HDL cholesterol levels, some coagulation parameters, mean blood pressure values and myocardial necrosis patterns.


RESULTS
L-NAME lowered plasma nitric oxide values, increased plasma total cholesterol and decreased HDL cholesterol levels, enhanced the amount of plasma fibrinogen, shortened prothrombin times, elevated the mean blood pressure values and caused the appearance of cardiac necrosis markers (c-troponin I, creatine kinase) in plasma and coagulative necrosis lesions in the myocardium. The administration of nitroglycerine to rabbits treated with L-NAME increased plasma nitric oxide levels and reversed the biochemical lesions caused by L-NAME.


CONCLUSIONS
Our data show that the studied alterations in cholesterol values, coagulation parameters, increased mean blood pressure values and myocardial necrosis markers are strictly related to modified plasma nitric oxide levels, and that the regulation of nitric oxide metabolism affects the presence or absence of some coronary disease risk factors (lipid, coagulation and blood pressure alterations) and plasma indicators of myocardial necrosis.
Pinelli
Arnaldo
A
Department of Pharmacology, Chemotherapy and Medical Toxicology, Milan, Italy. arnaldo.pinelli@unimi.it
Trivulzio
Silvio
S
Tomasoni
Livio
L
Bertolini
Boris
B
Brenna
Sergio
S
Bonacina
Edgardo
E
Accinni
Roberto
R
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008297:Male; D009206:Myocardium / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009336:Necrosis; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology*; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D015415:Biomarkers; D008076:Cholesterol, HDL; D014665:Vasodilator Agents; D009569:Nitric Oxide; D002784:Cholesterol; D005996:Nitroglycerin; D019331:NG-Nitroarginine Methyl Ester