Effects of renal medullary and intravenous norepinephrine on renal antihypertensive function

Increasing renal arterial pressure activates at least 3 antihypertensive me chanisms: reduced renin release, pressure natriuresis, and release of a put ative renal medullary depressor hormone. To examine the role of renal medul lary perfusion in these mechanisms, we tested the effects of the infusion o f norepinephrine, either infusion into the renal medullary interstitium or intravenous infusion, on responses to increased renal arterial pressure in pentobarbital-anesthetized rabbits. We used an extracorporeal circuit, whic h allows renal arterial pressure to be set to any level above or below syst emic arterial pressure. With renal arterial pressure initially set at 65 mm Hg, intravenous and medullary interstitial norepinephrine (300 ng.kg(-1).m in(-1)) similarly increased mean arterial pressure (by 12% to 17% of baseli ne) and reduced total renal blood flow (by 16% to 17%) and cortical perfusi on (by 13% to 19%), but only medullary norepinephrine reduced medullary per fusion (by 28%). When renal arterial pressure was increased to approximate to 160 mm Hg, in steps of approximate to 65 mm Hg, urine output and sodium excretion increased exponentially, and plasma renin activity and mean arter ial pressure fell. Medullary interstitial but not intravenous norepinephrin e attenuated the increased diuresis and natriuresis and the depressor respo nse to increased renal arterial pressure. This suggests that norepinephrine can act within the renal medulla to inhibit these renal antihypertensive m echanisms, perhaps by reducing medullary perfusion. These observations supp ort the concept that medullary perfusion plays a critical role in the long- term control of arterial pressure by its influence on pressure diuresis/nat riuresis mechanisms and also by affecting the release of the putative renal medullary depressor hormone.