Effects of Renal Medullary and Intravenous Norepinephrine on Renal Antihypertensive Function

Abstract

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 ⅐ kg Ϫ1 ⅐ min Ϫ1 ) 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 Ϸ160 mm Hg, in steps of Ϸ65 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. Key Words: kidney medulla Ⅲ laser-Doppler flowmetry Ⅲ norepinephrine Ⅲ natriuresis Ⅲ renal circulation I t has been hypothesized that the level of medullary blood flow (MBF) is an important determinant of urinary sodium excretion (U Na ϩ V) and, indeed, may be the key initiating factor in the pressure natriuresis response. 1 In turn, the impact of MBF on the pressure natriuretic mechanism provides an explanation for the effects of chronic changes in MBF on the long-term control of arterial pressure. 1 Thus, in rats, chronic reductions in MBF shift the pressure natriuresis relation toward higher pressures and lead to hypertension in normotensive animals. Conversely, chronic increases in MBF shift the pressure natriuresis relation toward lower pressures and ameliorate hypertension in spontaneously hypertensive rats. 1 From studies using an extracorporeal circuit in anesthetized rabbits, 2 we recently obtained preliminary evidence indicating that influences on the release and/or actions of the putative renal medullary depressor hormone might also contribute to the impact of MBF on the long-term control of arterial pressure. In this model, 3 major renal antihypertensive mechanisms can be studied simultaneously. Thus, when renal arterial ...

Autoregulation of renal medullary blood flow in rabbits

“…Baseline hemodynamic variables were similar to those we observed previously (7,20,43) (Table 1). In protocol 2A, MAP measured from the ear artery was 18 Ϯ 3 mmHg less than RAP measured from the descending aorta, presumably reflecting the greater upstream vascular resistance in the ear artery.…”

“…1), urine flow, and sodium excretion. Data regarding RBF, [ 3 H]inulin clearance, sodium excretion, urine flow, and plasma renin activity from protocol 1, but not laser-Doppler flux (LDF), have been published elsewhere (7,43).…”

“…The extracorporeal circuit has been described in detail (5,7,11,43). Briefly, blood was withdrawn at 90 ml/min from the aorta with a roller pump (Masterflex model 7521-45, Barnant, Barrington, IL) and returned to the rabbit via the vena cava and renal artery.…”

“…After equilibration, RAP was set at 65, 85, 110, 130, and 160 mmHg for consecutive 20-min periods (protocol 1A). Urine volume and sodium excretion were determined as previously described (7,43).…”

“…This does not necessarily hold true for the kidney, in which the volume density of red blood cells is 3-5% (41). Signals were amplified and recorded as previously described (7,20). Levels of RBF (1.7 Ϯ 0.1 ml/min), CLDF (14 Ϯ 2 units), MLDF (12 Ϯ 1 units for the attached probe and 12 Ϯ 1 units for the externally fixed probe), and concentration (20 Ϯ 3 units for the attached probe and 48 Ϯ 5 for the externally fixed probe) were measured during the 60 s after the animal was killed.…”