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L‐arginine Supplementation Reduces Local Cardiac Noradrenergic Neurotransmission in Spontaneously Hypertensive Rats
Author(s) -
Lee Chee Wan,
Chan Keith M,
Paterson David J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.953.5
Subject(s) - medicine , endocrinology , norepinephrine , nitric oxide , chemistry , arginine , cyclic guanosine monophosphate , guanosine , nitric oxide synthase , dopamine , amino acid , biochemistry
Hypertension is associated with noradrenergic hyperactivity. We hypothesised that L‐arginine (L‐arg) supplementation may reduce cardiac noradrenergic hyperactivity in spontaneously hypertensive rats (SHR) via upregulation of nitric oxide synthase (NOS) – cyclic guanosine monophosphate (cGMP) pathway. SHR and Wistar Kyoto rats (WKY) aged 16 weeks were fed with L‐arg (10g/L in drinking water). A control group received no supplementation. A week later, the isolated right atria were used for measurement of electrically evoked [ 3 H]norepinephrine (NE) release. The SHR control group had a significantly lower plasma L‐arg. NE release from the SHR control was higher than the WKY control (340±27% vs 273±25%, p<0.05), but was reduced to 259±13% with L‐arg (p<0.01). Addition of soluble guanylate cyclase (sGC) inhibitor, 1H‐(1,2,4)oxadiazolo(4,3‐a)quinoxaline‐1‐one (10 μM), to organ bath caused a proportionally higher increase of NE release in the L‐arg fed SHR (to 386%) compared with the non‐fed SHR (to 431%) (p<0.01 for paired analysis; p=NS between groups). L‐arg feeding did not reduce NE release in the WKY. Atrial cGMP was lower in the SHR compared with the WKY (2.4±0.4 pmol/mg vs 4.4±0.5 pmol/mg, p<0.05), but increased to 4.1±0.6 pmol/mg protein (p<0.05) with L‐arg. In conclusion, we have shown that L‐arg supplementation corrects the cardiac noradrenergic hyperactivity in the SHR via the NOS‐sGC‐cGMP pathway.