Systemic hypotensive response to protamine following chronic inhibition of nitric oxide synthase in rats.
OBJECTIVE
The aims of the present studies were to determine whether the systemic hypotensive response to protamine was modified in rats pre-treated for two weeks with the nitric oxide synthase inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME), and to evaluate the inhibitory effect of heparin on the systemic hypotensive response to protamine in vivo.


METHODS
Male rats were randomly assigned into four groups. Normal saline 12 microliters.day-1, D-NAME (an inactive enantiomer of L-NAME), 10 mg.kg-1, L-NAME, 1 or 10 mg.kg-1.day-1 i.p. was administered for two weeks and the haemodynamic changes were measured after protamine administration. In another experiment, male rats were assigned to two groups. In one, the heparin group, protamine was administered after heparin had been administered and in the other, protamine group, protamine alone was administered.


RESULTS
L-NAME inhibited the decrease in systemic arterial pressure after protamine administration (P < 0.05), but D-NAME had no effect. Also, heparin reduced the decrease in systemic arterial pressure after protamine (P < 0.05).


CONCLUSIONS
Nitric oxide is mainly responsible for mediation of the systemic hypotensive response to protamine which is also reduced by heparin.
Department of Anesthesiology, Hiraga General Hospital, Japan.
H
H
Komatsu
K
K
Enzan
S
S
Matsuura
S
S
Kurosawa
H
H
Mitsuhata
D000704:Analysis of Variance; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use; D006494:Heparin Antagonists / Q000009:adverse effects*; D007022:Hypotension / Q000139:chemically induced / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011479:Protamines / Q000009:adverse effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000925:Anticoagulants; D004791:Enzyme Inhibitors; D006494:Heparin Antagonists; D011479:Protamines; D006493:Heparin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester