L‐arginine Supplementation Reduces Local Cardiac Noradrenergic Neurotransmission in Spontaneously Hypertensive Rats

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 Hnorepinephrine (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.