Interleukin-1 beta and neurogenic control of blood pressure in normal ratsand rats with chronic renal failure

Increased sympathetic nervous system (SNS) activity plays a role in the gen esis of hypertension in rats with chronic renal failure (CRF). The rise in central SNS activity is mitigated by increased local expression of neuronal nitric oxide synthase (NOS) mRNA and NO2/NO3 production. Because interleuk in (IL)-1 beta may activate nitric oxide in the brain, we have tested the h ypothesis that IL-1 beta may modulate the activity of the SNS via regulatio n of the local expression of neuronal NOS (nNOS) in the brain of CRF and co ntrol rats. To this end, we first found that administration of IL-1 beta in the lateral ventricle of control and CRF rats decreased blood pressure and norepinephrine (NE) secretion from the posterior hypothalamus (PH) and inc reased NOS mRNA expression. Second, we observed that an acute or chronic in jection of an IL-1 beta -specific antibody in the lateral ventricle raised blood pressure and NE secretion from the PH and decreased NOS mRNA abundanc e in the PH of control and CRF rats. Finally, we measured the IL-1 beta mRN A abundance in the PH, locus coeruleus, and paraventricular nuclei of CRF a nd control rats by RT-PCR and found it to be greater in CRF rats than in co ntrol rats. In conclusion, these studies have shown that IL-1 beta modulate s the activity of the SNS in the central nervous system and that this modul ation is mediated by increased local expression of nNOS mRNA.