Hypotensive effect of agmatine, arginine metabolite, is affected by NO synthase.
The metabolites of arginine were recently shown to be involved in cardiovascular control. The study addresses the general cardiovascular response of anaesthetized rats to agmatine, a decarboxylated arginine. The relation between two arginine metabolic pathways governed by arginine decarboxylase and nitric oxide synthase was investigated. Intravenous administration of agmatine 30 and 60 microM/0.1 ml saline elicited remarkable hypotension of 42.6+/-4.6 and 70.9+/-6.5 mm Hg, respectively. The hypotension was characterized by long duration with half-time of return 171.6+/-2.9 and 229.2+/-3.8 s, respectively. The time of total blood pressure BP recovery was about 10 min. Dose-dependent relaxation to agmatine was also found in aorta rings in vitro. Both doses of agmatine administered 60-180 min after NO synthase inhibition L-NAME 40 mg/kg i.v. caused greater hypotension 59.0+/-7.6 and 95.8 8.8 mm Hg P<0.01 both compared to animals with intact NO synthase, but this was accompanied by a significant shortening of the half-time of BP return. If agmatine was administered to hypertensive NO-deficient rats treated with 40 mg/kg/day L-NAME for 4 weeks, similar significant enhancement of hypotension was observed at both agmatine doses, again with a significant shortening of half-time of BP return. It can be summarized that the long-lasting hypotension elicited by agmatine was amplified after acute or chronic NO synthase inhibition, indicating a feedback relation between the two metabolic pathways of arginine.
Gerová
M
M
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Sienkiewiczova 1, 813 71 Bratislava, Slovak Republic. gerova@unpf.savba.sk
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D000376:Agmatine / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology; D001120:Arginine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007022:Hypotension / Q000139:chemically induced / Q000201:enzymology*; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000376:Agmatine; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester