title: Effects of renal medullary and intravenous norepinephrine on renal antihypertensive function.
abstract: Increasing renal arterial pressure activates at least 3 antihypertensive mechanisms: reduced renin release, pressure natriuresis, and release of a putative renal medullary depressor hormone. To examine the role of renal medullary perfusion in these mechanisms, we tested the effects of the infusion of 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, which allows renal arterial pressure to be set to any level above or below systemic arterial pressure. With renal arterial pressure initially set at 65 mm Hg, intravenous and medullary interstitial norepinephrine (300 ng. kg(-1). min(-1)) similarly increased mean arterial pressure (by 12% to 17% of baseline) and reduced total renal blood flow (by 16% to 17%) and cortical perfusion (by 13% to 19%), but only medullary norepinephrine reduced medullary perfusion (by 28%). When renal arterial pressure was increased to approximately 160 mm Hg, in steps of approximately 65 mm Hg, urine output and sodium excretion increased exponentially, and plasma renin activity and mean arterial pressure fell. Medullary interstitial but not intravenous norepinephrine attenuated the increased diuresis and natriuresis and the depressor response to increased renal arterial pressure. This suggests that norepinephrine can act within the renal medulla to inhibit these renal antihypertensive mechanisms, perhaps by reducing medullary perfusion. These observations support the concept that medullary perfusion plays a critical role in the long-term control of arterial pressure by its influence on pressure diuresis/natriuresis mechanisms and also by affecting the release of the putative renal medullary depressor hormone.
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria, Australia. anabela.correia@med.monash.edu.au
authors.forename: A G
authors.initials: AG
authors.lastname: Correia
authors.forename: A C
authors.initials: AC
authors.lastname: Madden
authors.forename: G
authors.initials: G
authors.lastname: Bergström
authors.forename: R G
authors.initials: RG
authors.lastname: Evans
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D001794:Blood Pressure; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology*; D007679:Kidney Medulla / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D012079:Renal Circulation; D014662:Vasoconstrictor Agents / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D009638:Norepinephrine