Hypotensive Effect of
Agmatine, Arginine Metabolite,
is Affected by NO Synthase
M. GEROVÁ, J. TÖRÖK
Institute of Normal and Pathological Physiology, Slovak Academy
of Sciences, Bratislava,
Slovak Republic
Received June 9, 2003
Accepted September 29, 2003
Summary
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 μM/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 229.23.8 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.
Key words
Agmatine • Hypotension • NO synthase • NO-deficient hypertension
• Aorta relaxation
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