Two-compartment model of inner medullary vasculature supports dual modes of vasopressin-regulated inner medullary blood flow

Abstract

The outer zone of the renal inner medulla (IM) is spatially partitioned into two distinct interstitial compartments in the transverse dimension. In one compartment (the intercluster region), collecting ducts (CDs) are absent and vascular bundles are present. Ascending vasa recta (AVR) that lie within and ascend through the intercluster region (intercluster AVR are designated AVR(2)) participate with descending vasa recta (DVR) in classic countercurrent exchange. Direct evidence from former studies suggests that vasopressin binds to V1 receptors on smooth muscle-like pericytes that regulate vessel diameter and blood flow rate in DVR in this compartment. In a second transverse compartment (the intracluster region), DVR are absent and CDs and AVR are present. Many AVR of the intracluster compartment exhibit multiple branching, with formation of many short interconnecting segments (intracluster AVR are designated AVR(1)). AVR(1) are linked together and connect intercluster DVR to AVR(2) by way of sparse networks. Vasopressin V2 receptors regulate multiple fluid and solute transport pathways in CDs in the intracluster compartment. Reabsorbate from IMCDs, ascending thin limbs, and prebend segments passes into AVR(1) and is conveyed either upward toward DVR and AVR(2) of the intercluster region, or is retained within the intracluster region and is conveyed toward higher levels of the intracluster region. Thus variable rates of fluid reabsorption by CDs potentially lead to variable blood flow rates in either compartment. Net flow between the two transverse compartments would be dependent on the degree of structural and functional coupling between intracluster vessels and intercluster vessels. In the outermost IM, AVR(1) pass directly from the IM to the outer medulla, bypassing vascular bundles, the primary blood outflow route. Therefore, two defined vascular pathways exist for fluid outflow from the IM. Compartmental partitioning of V1 and V2 receptors may underlie vasopressin-regulated functional compartmentation of IM blood flow.

Fig. 1.

Transverse sections showing one single primary collecting duct (CD) cluster (from Fig. 2A in Ref. 28) from four progressively deeper levels below the outer medullary (OM)-inner medullary (IM) boundary [CDs, aquaporin-2 (AQP2)/blue; descending vasa recta (DVR), urea transporter B (UT-B)/green; ascending vasa recta AVR₁ and AVR₂, PV-1/red]. The inner white irregular polygon of each image outlines the approximate intracluster region. The outer white boundary of each image is the intercluster Euclidean distance map (EDM) border; the EDM border delimits the intercluster region. Scale bars = 50 μm.

Fig. 2.

Cross-sectional areas of secondary clusters 1 (A) and 2 (B) at progressively deeper levels below the OM-IM boundary. Total area (□), intercluster area (●), and intracluster area (○).

Fig. 3.

Number densities of IM blood vessels and vessel/CD ratios. A: number of PV-1-positive vessels, number of PV-1-positive vessels abutting CDs, and ratio of number of PV-1-positive vessels abutting CD/number of CDs for random cross-sectional areas of the IM from 3 kidneys. Values are means ± SE. Ratio means are not significantly different along the corticopapillary axis (ANOVA with Duncan's post hoc test; P < 0.05). B: vessel number densities and AVR₁/CD ratios for CD clusters 1 and 2. Contrast with AVR₂ of the same tissue in Fig. 4 in Ref. .

Fig. 4.

Diagram of vasa recta architecture in the outer zone of the IM. The UT-B-positive (light shading, nonfenestrated) DVR descends along the corticopapillary axis. The UT-B-positive segment overlaps (small bracket) with PV-1 (dark shading, fenestrated) and is continuous with a descending PV-1-positive, UT-B-negative DVR (large bracket) (28). This PV-1-positive segment is continuous with AVR₁, which lie within the CD cluster (intracluster region). AVR₁ connect to AVR₂ in vascular bundles of the intercluster region. A number of AVR₁ also ascend directly from the outermost IM into the innermost inner stripe of the OM. Arrows denote blood flow direction. AVR₁, PV-1-positive intracluster AVR and interconnecting capillaries that do abut CDs; AVR₂, ascending, PV-1-positive intercluster vessels that do not abut CDs, and do or do not abut DVR.

Fig. 5.

Length histograms of fenestrated vessels in CD cluster 1 (as shown in Fig. 2A in Ref. 28). A: axial lengths of 62 AVR₂ (intercluster AVR). B: axial lengths of 324 AVR₁ that form an intracluster network.

Fig. 6.

Lengths of AVR₁ and AVR₂ in secondary CD clusters 1 (A) and 2 (B) (as shown in Fig. 2A in Ref. 28). Values are means + SE. Horizontal lines show median lengths of vessels for each category. Lengths of AVR₁ are significantly shorter than AVR₂. P < 0.05, Student's 2-sample t-test.

Fig. 7.

Mean distances to nearest CD for AVR₁ and AVR₂ in secondary CD clusters 1 (A) and 2 (B) (as shown in Fig. 2A in Ref. 28). Distances (means + SE, n = 10) were averaged for the entire ascent of a random selection of vessels from each cluster. Distances of AVR₁ to nearest CD are significantly shorter than distances of AVR₂ to nearest CD. P < 0.05, Student's 2-sample t-test.

Fig. 8.

AVR₁ ascending directly from the outermost IM into the innermost inner stripe of the OM [CDs, AQP2/blue; ascending thin limbs of Henle's loop (ATLs) in the IM and thick ascending limbs in the OM, ClC-K/green; DVR, UT-B/yellow; AVR₁ and AVR₂, PV-1/red]. In B autofluorescence in thick ascending limbs appears as light blue-gray. A: thick ascending limbs (OM) and ATLs (IM). B: fenestrated vessels at the OM-IM boundary (AVR). C and D: enlarged boxed areas. E: plane of tissue section through the OM-IM boundary. Scale bars = 40 μm.