[Inhibitors of arginase in the L-arginine metabolic pathway as a new class of antihypertensive drugs: effect of carbamide on lipid oxidative metabolism and on vessel tonus during arterial hypertension].
Have studied action of chronic urea--an arginase inhibitor--introduction (40 mg/kg, 28 days) on blood pressure, endothelium-dependent reactions of aorta smooth muscle cells (SMC) and nonenzymatic (contents of diene conjugates and H2O2) and enzymatic (contents of free arachidonic acid and vasoconstrictic eicosanoids LTC4 and TXA2) oxidizing lipid metabolism of heart, aorta, plasma and erythrocytes of spontaneously hypertensive rats. Have shown, that urea down regulate blood pressure without any normalization of endothelium-dependent reactions of SMC of aorta and down regulate both enzymatic and nonenzymatic oxidizing lipid metabolism. Down regulation of two alternative (by cyclooxygenase and by lipoxygenase) enzymatic pathways of free arachidonic acid oxidizing metabolism by urea can be one of mechanisms of its antihypertensive action. The possibility of urea use at hypertension and various pathophysiological conditions are discussed.
Sahach
V F
VF
A.A. Bogomolets Institute of Physiology, National Academy of Science of Ukraine, Kiev.
Kotsiuruba
A V
AV
Baziliuk
O V
OV
Mehed'
O F
OF
Bykhanevich
O M
OM
Hula
N M
NM
Stepanenko
L H
LH
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects; D001119:Arginase / Q000037:antagonists & inhibitors*; D001120:Arginine / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy*; D050356:Lipid Metabolism; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D014508:Urea / Q000494:pharmacology*
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D014508:Urea; D001120:Arginine; D001119:Arginase
Inhibitory arhinaznoho shliakhy metabolizmu L-arhininu iak novyĭ klas antyhipertenzyvnykh spoluk: diia karbamidu na okysnyĭ metabolizm lipidiv i sudynnyĭ tonus pry arterial'niĭ hipertenziï.