Diversity of responses of renal cortical and medullary blood flow to vasoconstrictors in conscious rabbits

Abstract

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.

Quantification of renal perfusion: Comparison of arterial spin labeling and dynamic contrast‐enhanced MRI

“…In an orthotopic transplantation study, a flow rate of 3.7 6 1.0 mL/g/min was used to perfuse isolated rabbit kidneys to maintain homeostasis (27). On comparing medullary to cortical perfusion, several studies reported a 3-fold decrease in the medulla, similar to our results, but provided only relative perfusion units (28,29). MRI studies of renal perfusion quantification in rabbits are not available for comparison, but parallels can be drawn to several DCE-MRI and ASL human studies given the similar perfusion rates in rabbits and humans.…”

“…Quantification of perfusion in the renal medulla using MRI is challenging. Although our ASL medulla perfusion estimate of 1.53 6 0.35 mL/g/min agrees with the 3-fold reduction relative to cortical perfusion reported in the rabbit kidney (28,29), estimating medulla perfusion is prone to partial volume effects. This source of error, which is greatest near the boundary of the cortex as well as at the interface of the inner and outer medulla, may account for the reported variation (0.55 6 0.25 to 2.23 6 0.76 mL/g/min in humans (16,33)) from ASL approaches.…”

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

“…Second, differential regional regulation of blood flow in the kidney has been measured during acute NOS inhibition in anesthetized46 and conscious animals47 and in humans 48. Vascular resistance in kidneys of L‐NAME–treated rats was greater in the medulla than in the cortex, which was caused by a shift of intrarenal blood flow and hence oxygen delivery from medulla to cortex 49.…”

Disparate Roles of AT 2 Receptors in the Renal Cortical and Medullary Circulations of Anesthetized Rabbits

“…For example, high-dose intravenous infusions of angiotensin II in rabbits transiently increase MLDF, which returns to control levels within 10 to 20 minutes despite continuous delivery of angiotensin II. 3,42 When doses of angiotensin II are increased from a threshold level, MLDF remains remarkably stable in the face of profound reductions in RBF and CLDF. 10 When given as a renal-arterial bolus, angiotensin II decreases total RBF and CLDF but has a biphasic effect on MLDF, with an initial decrease followed by an increase.…”

“…In rats and rabbits, infusions of angiotensin II reduce total renal blood flow (RBF) and cortical blood flow but have a lesser effect on medullary blood flow (MBF). [2][3][4][5] Angiotensin II can even increase MBF, especially when administered as a bolus. 6 -8 Nitric oxide synthase and/or cyclooxygenase blockade can enhance angiotensin II-induced reductions in MBF and abolish angiotensin II-induced increases in MBF, both of which are chiefly AT 1 mediated.…”