The kidney and the neurogenic control of blood pressure in renal disease.

Hypertension is very common in patients with chronic renal failure (CRF) and it contributes to morbidity and mortality as well as to the progression of renal disease. Several mechanisms may play a role in the pathogenesis of hypertension in CRF, but the best known are sodium retention and activation of the renin-angiotensin-aldosterone system. More recently, evidence has accumulated to support a role for increased sympathetic nervous system (SNS) activity in the genesis of hypertension associated with CRF. Our laboratory findings indicate that specific renal injuries, caused by 5/6 nephrectomy and/or phenol injection in the kidney, activate renal afferent pathways that connect with integrative structures in the brain involved in the regulation of SNS activity and blood pressure. This results in a rise in blood pressure sustained by noradrenergic mechanisms. Our laboratory has also shown that the rise in central SNS activity is mitigated by increased local expression of nitric oxide synthase (NOS)-mRNA and nitric oxide (NO) production, and by upregulation of interleukin-1beta.