A new model of neurogenic hypertension caused by renal injury: pathophysiology and therapeutic implications.

Increasing evidence indicates that afferent impulses from injured kidney may activate areas of the brain involved in the noradrenergic regulation of blood pressure and largely contribute to the development and maintenance of hypertension associated with renal diseases. A new model of hypertension developed in our laboratory by an intrarenal injection of phenol has largely substantiated this hypothesis. Our studies also provide evidence that complex interactions exist between interleukin (IL)-1Beta and nitric oxide in the regulation of central sympathetic nervous system (SNS) activity and blood pressure. Following renal injury with phenol, the abundance of IL-1Beta and neuronal isoform of nitric oxide synthase (nNOS) in the brain decreased, and this may mediate the rise in SNS activity. Finally, our studies provide evidence that locally produced angiotensin II in the brain may ultimately mediate the downregulation of IL-1Beta and nNOS and result in increased SNS activity and hypertension in the phenol-renal-injury model.