The role of renal sympathetic nerve activity (RSNA) in the physiological regulation of medullary blood flow (MBF) remains ill defined, yet regulation of MBF may be crucial to long-term arterial pressure regulation. To investigate the effects of reflex increases in RSNA on intrarenal blood flow distribution, we exposed pentobarbital sodium-anesthetized, artificially ventilated rabbits (n = 7) to progressive hypoxia while recording RSNA, cortical blood flow (CBF), and MBF using laser-Doppler flowmetry. Another group of animals with denervated kidneys (n = 6) underwent the same protocol. Progressive hypoxia (from room air to 16, 14, 12, and 10% inspired O(2)) significantly reduced arterial oxygen partial pressure (from 99 +/- 3 to 65 +/- 2, 51 +/- 2, 41 +/- 1, and 39 +/- 2 mmHg, respectively) and significantly increased RSNA (by 8 +/- 3, 44 +/- 25, 62 +/- 21, and 76 +/- 37%, respectively, compared with room air) without affecting mean arterial pressure. There were significant reductions in CBF (by 2 +/- 1, 5 +/- 2, 11 +/- 3, and 14 +/- 2%, respectively) in intact but not denervated rabbits. MBF was unaffected by hypoxia in either group. Thus moderate reflex increases in RSNA cause renal cortical vasoconstriction, but not at vascular sites regulating MBF.

The medullary microcirculation receives only about 10% of total renal blood flow, but plays a critical role in long-term arterial pressure regulation, so we need to better understand its regulation. Although there is evidence that circulating and locally acting hormones can differentially affect cortical and medullary blood flow in anaesthetized animals, there is little information from studies in conscious animals. This study is aimed (i) to develop a method for chronic measurement of cortical and medullary blood flow in conscious rabbits, and (ii) to test whether renal cortical and medullary blood flow can be differentially affected by intravenous (i.v.) infusions of various vasoconstrictor hormones in conscious rabbits. At preliminary operations, rabbits were equipped with single-fibre laser-Doppler flowprobes in the (left) renal cortex and medulla, and Transonic flowprobes for measuring cardiac output and renal blood flow. Intravenous angiotensin II (300 ng kg(-1) min(-1)), [Phe2,Ile3,Orn8]-vasopressin (30 ng kg(-1) min(-1)), noradrenaline (300 ng kg(-1) min(-1)), endothelin-1 (20 ng kg(-1) min(-1)) and N G-nitro-L-arginine (10 mg kg(-1)) increased mean arterial pressure (by 10-45% of baseline) and reduced heart rate (by 16-35%) and cardiac output (by 16-45%). Consistent with previous observations in anaesthetized rabbits, all treatments except [Phe2,Ile3, Orn8]-vasopressin reduced renal blood flow (13-63%) and cortical blood flow (16-47%), but medullary blood flow was significantly reduced only by [Phe2,Ile3,Orn8]-vasopressin (41%) and N G-nitro-L-arginine (42%). The diversity of these responses of cortical and medullary blood flow to i.v. infusions of vasoconstrictors provides further evidence for physiological roles of circulating and local hormones in the differential regulation of regional kidney blood flow.

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 ...

Endogenous ETs act at ET(A)-receptors to reduce MBF and CBF, but ET(B)-receptors have little direct role in physiological control of renal haemodynamics. Bolus doses of ET-1 act at ET(B)-receptors in the kidney to increase MBF. The effects of bolus ET-1 on the cortical vasculature appear to result from the competing influences of ET(A)-mediated vasoconstriction and ET(B)-mediated vasodilatation.