Losartan reduces sympathetic nerve outflow from the brain of rats with chronic renal failure

Vito M Campese, Shaohua Ye, Rex H Truong, Michael Gamburd
2000 Journal of the Renin-Angiotensin-Aldosterone System  
Sympathetic nervous system (SNS) activity, measured by norepinephrine (NE) turnover rate, was greater in the posterior hypothalamic (PH) nuclei, the paraventricular nuclei (PVN), and the locus coeruleus (LC) of 5/6 nephrectomised (CRF) rats than of control rats. NE secretion from the PH was also greater in CRF than in control rats. These findings demonstrate that SNS activity plays an important role in the genesis of hypertension associated with CRF. The increase in central SNS activity was
more » ... gated by increased local expression of nitric oxide synthase (NOS)-mRNA and nitric oxide (NOx) production. Because angiotensin II may stimulate the central SNS, we tested the hypothesis that losartan, a specific angiotensin II AT 1 -receptor antagonist, may lower blood pressure (BP), at least in part, by central noradrenergic inhibition. To this end, we studied two groups of CRF rats. One group received losartan (10 mg/kg body weight) in drinking water between the 3rd and 4th week after nephrectomy, the second group received drinking water without losartan. SNS activity was measured by NE secretion from the PH using the microdialysis technique. NOS-mRNA gene expression was also measured by RT-PCR in the PH, PVN, and LC of CRF and control rats. Losartan reduced systolic BP from 184±3.7 to 152±3.1 mmHg and NE secretion from the PH from 340±9.7 to 247±4.8 pg/ml. CRF rats treated with losartan manifested a significant (p<0.01) increase in the expression of nNOS-mRNA in the PH (from 84±1.2 to 99±2.6), the PVN (from 44±1.5 to 63±2.
doi:10.3317/jraas.2000.026 pmid:11967814 fatcat:7ie5k5raezb47lux6v6xz7kqwa