E. Nava et al., CHANGES IN NITRIC-OXIDE RELEASE IN-VIVO IN RESPONSE TO VASOACTIVE SUBSTANCES, British Journal of Pharmacology, 119(6), 1996, pp. 1211-1216
1 Changes in the release of nitric oxide (NO) in vivo were studied in
rats following the administration of endothelium-dependent and -indepe
ndent vasodilators as well as the NO synthesis inhibitor, N-G-nitro-L-
arginine methyl ester (L-NAME). NO production was assessed by measurin
g variations of nitrate in plasma by capillary ion analysis. 2 Intrave
nous administration of the endothelium-dependent vasodilators, bradyki
nin (2 and 10 mu g kg(-1) min(-1)) or substance P (0.3-3 mu g kg(-1) m
in(-1)) caused a transient dose-dependent hypotension followed by an i
ncrease in plasma nitrate concentration (maximal increments: 33+/-5% a
nd 38+/-6%, for bradykinin and substance P, respectively). Prior admin
istration of L-NAME (10 mg kg(-1) min(-1)) inhibited the hypotension a
nd increase in plasma nitrate caused by these substances. Intravenous
administration of sodium nitrate (200 mu g kg(-1)) also produced a tra
nsitory elevation in plasma nitrate which was similar in magnitude as
that caused by the vasodilators. A rapid and transitory increment in p
lasma nitrate was observed after i.v. administration of authentic NO (
400 mu g kg(-1)). 3 Rats receiving the endothelium-dependent vasodilat
ors, prostacyclin (0.6 mu g kg(-1) min(-1)) or adenosine (3 mg kg(-1)
min(-1)) intravenously showed a drop in blood pressure paralleled by a
decrease in plasma nitrate (maximal decreases: 34+/-5% and 24+/-4%, f
or prostacyclin and adenosine, respectively). A similar effect on the
plasmatic concentration of nitrate was observed when L-NAME (10 mg kg(
-1) min(-1), i.v.) was administered to the animals. 4 This study demon
strates that (i) changes in plasma nitrate can be detected in vivo aft
er stimulation or inhibition of NO synthase, (ii) an increased product
ion of NO, measured as plasma nitrate, is related to the hypotension c
aused by bradykinin and substance P and (iii) a diminished concentrati
on of plasmatic nitrate is associated to the hypotension induced by ad
enosine or prostacyclin (endothelium-independent vasodilators), sugges
ting that the L-arginine: NO pathway is capable of rapid down-regulati
on in response to a fall in blood pressure.