Cardiovascular effects of noradrenaline in hypovolemic haemorrhage: role of inducible nitric oxide synthase.
Hypovolemia has been associated with the induction of nitric oxide synthase which is believed to result in an over-production of nitric oxide. In the present study, we have examined the effects of noradrenaline following haemorrhage on cardiac output, blood pressure, mean circulatory filling pressure and vascular resistance in anaesthetized rats after pre-treatment with nitric oxide synthase inhibitor, L-N6-(1-iminoethyl)lysine or dexamethasone. Hypovolemic haemorrhage resulted in induction of nitric oxide synthase, as measured in lungs, and both dexamethasone and L-N6-(1-iminoethyl)lysine inhibited the activity of the inducible form of nitric oxide synthase. An infusion of noradrenaline significantly increased cardiac output, blood pressure and mean circulatory filling pressure in animals pre-treated with L-N6-(1-iminoethyl)lysine and dexamethasone when compared with saline pre-treatment. In addition, the administration of noradrenaline significantly reduced venous resistance in animals pre-treated with L-N6-(1-iminoethyl)lysine when compared with saline pre-treatment. The results of this investigation indicated that the impact of noradrenaline on cardiac output, blood pressure and mean circulatory filling pressure was greater in hypovolemic rats treated with L-N6-(1-iminoethyl)lysine or dexamethasone. In addition, we found that in the hypovolemic state, the greater increase in cardiac output during the infusion of noradrenaline after inhibition of nitric oxide synthase was predominantly due to reduced resistance to venous return.
Tabrizchi
R
R
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada. rtabrizc@morgan.ucs.mun.ca
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; C090663:N(6)-(1-iminoethyl)lysine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D008239:Lysine; D009638:Norepinephrine