NITRIC-OXIDE (NO) MODULATES THE NEUROGENIC CONTROL OF BLOOD-PRESSURE IN RATS WITH CHRONIC-RENAL-FAILURE (CRF)

Increased sympathetic nervous system (SNS) activity plays a role in th e genesis of hypertension in rats with chronic renal failure (CRF). Be cause nitric oxide (NO) modulates the activity of the SNS, a deficit o f NO synthesis could be responsible for the increased SNS activity in these animals. In the present study, we evaluated the effects of L-arg inine and L-NAME an blood pressure and SNS activity in Sprague Dawley 5/6 nephrectomized or sham-operated rats. SNS activity was determined by measuring norepinephrine turnover rate in several brain nuclei invo lved in the regulation of blood pressure. In the same brain nuclei, we measured NO content and nitric oxide synthase (NOS) gene expression b y semiquantitative measurements of NOS mRNA reverse transcription poly merase chain reaction. In CRF rats, norepinephrine turnover rate was i ncreased in the posterior hypothalamic nuclei, locus coeruleus, parave ntricular nuclei, and the rostral ventral medulla, whereas NOS mRNA ge ne expression and NO2/NO3 content were increased in all brain nuclei t ested. L-NAME increased blood pressure and NE turnover rate in several brain nuclei of both control and 5/6 nephrectomized rats. In CRF rats , a significant relationship was present between the percent increment in NOS mRNA gene expression related to the renal failure, and the per cent increase in norepinephrine turnover rate caused by L-NAME. This s uggests that endogenous NO may partially inhibit the activity of the S NS in brain nuclei involved in the neurogenic regulation of blood pres sure, and this inhibition is enhanced in CRF rats. In summary, the inc rease in SNS activity in the posterior hypothalamic nuclei and in the locus caeruleus of CRF rats is partially mitigated by increased local expression of NOS m-RNA.