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Previous work has shown that the genes encoding each alpha1-adrenoceptor subtype are coexpressed throughout the peripheral vascular system. We have evaluated subtype-selective antibodies as tools to determine the extent of protein expression in arteries. The alpha1A-, alpha1B-, and alpha1D-adrenoceptors were detected in the medial layer of the aorta, caudal, femoral, iliac, renal, superior mesenteric, and mesenteric resistance arteries. In Rat1 fibroblasts expressing each subtype, immunoreactivity was noted both on the cell surface and in a perinuclear orientation. Intense alpha1B-adrenoceptor immunostaining was similarly localized in cultured femoral and renal vascular smooth muscle cells. Although the cellular localization appeared to be the same, immunoreactivity obtained with alpha1A- and alpha1D-adrenoceptors was much less intense than that with the alpha1B-adrenoceptor. The alpha1A-adrenoceptor selective agonist A-61603 was 22-fold more potent in activating renal artery contraction when compared with the femoral artery. The expression of each alpha1-adrenoceptor was significantly decreased by in vivo application of antisense oligonucleotides targeted against each subtype. Inhibition of the expression of only one, the alpha1A in renal and the alpha1D in femoral arteries, reduced the contractile response to naphazoline. The results show: 1) subtype-selective antibodies can be used in tissues and cell culture to localize the alpha1-adrenoceptor subtypes, 2) in addition to expression on the cell surface, the alpha1-adrenoceptors are expressed intracellularly, and 3) despite expression of all adrenoceptors, a single subtype mediates the contractile response in the femoral and renal arteries.

The effects of deamino-8-D-arginine vasopressin (desmopressin), a V2 receptor antidiuretic agonist, were studied in isolated rings from branches of renal arteries obtained from 22 patients undergoing nephrectomy. The rings were suspended in organ bath chambers for isometric recording of tension. In precontracted rings with norepinephrine (10(-6) to 3 x 10(-6) mol/L), desmopressin (10(-11) to 3 x 10(-7) mol/L) caused endothelium-dependent relaxation (81%+/-4% reversal of the initial contraction in arteries with endothelium; 20%+/-4% in arteries without endothelium; P < .05). The relaxation to desmopressin in rings with endothelium was reduced significantly by indomethacin (10(-6) mol/L) and unaffected by the inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (10(-4) mol/L). Two V1 receptor antagonists (a peptidic and a nonpeptidic) had no effect on desmopressin-induced relaxation. However, V2 receptor antagonists (three peptidic and a nonpeptidic) reduced significantly (P < .05) the maximal response to desmopressin. The results of this study show that desmopressin exerts powerful endothelium-dependent relaxation of human renal arteries, probably through stimulation of V2-like receptors that may bring about the release of dilating prostaglandins.

The effects of the small noncatalytic subunit of myosin light chain phosphatase (MLCPsr) on the Ca2+-induced contraction of smooth muscle were investigated in the Triton X-100-permeabilized porcine renal artery. The full-length recombinant chicken MLCPsr obtained by the bacterial expression system induced an additional contraction at a constant [Ca2+]i and shifted the [Ca2+]i-force relation curve to the left. A deletion mutant containing the N-terminal 78 amino acids of MLCPsr retained the full action, compared with the full-length MLCPsr, while the deletion of this region completely abolished its effect. The process of relaxation was also delayed by the fragment containing the N-terminal 78 amino acids. These results indicated that MLCPsr increases the Ca2+ sensitivity of the contractile apparatus while the N-terminal 78 amino acids are responsible for this effect in vascular smooth muscle., (Copyright 1999 Academic Press.)

Objectives: Thrombin generated at sites of vascular injury not only participates in the coagulation cascade but can also signal other events related to cell mitogenesis and migration. In this report, we investigated the effects of thrombin on the proliferation of human arterial smooth muscle cells (SMCs) in culture and its interaction with platelet-derived growth factor (PDGF)., Material and Methods: Human arterial SMCs originated from a renal artery were grown in cell culture. The effect of thrombin on DNA synthesis was evaluated by 3H-thymidine incorporation. The effect of thrombin on inositol-phosphate formation by SMCs was also analyzed as well as the binding of PDGF AA and BB to these cells. PDGF secretion was analyzed by radioimmunoassay (RIA)., Results: Exposure of cultured human SMCs to thrombin caused an increased rate of DNA synthesis in a dose-response manner, with a maximal stimulatory effect at a concentration of 2.0 U/mL. Thrombin was found to increase the accumulation of inositol phosphates and to increase the production of PDGF as measured by RIA. Exposure of cells to 2.0 U/mL thrombin resulted in a strong decrease in PDGF AA binding to PDGF receptors and did not change PDGF BB binding, probably indicating that PDGF alpha-receptors could be occupied by endogenously produced PDGF A., Conclusion: Thrombin stimulates human vascular SMC proliferation in a dose-response way, in part by the formation of inositol phosphates. The mechanism responsible for this effect involves, at least in part, an increased endogenous synthesis of PDGF.

We examined the infiltration of acutely rejecting renal allografts (DA-->LEW) by ED1+ and ED2+ macrophages and T lymphocytes at intervals of 24 h after transplantation. Donor and recipient macrophages were differentiated by MHC class II antigen expression in double-staining experiments with ED1. Proliferation was assayed after pulse-labelling with BrdU. We subdivided allograft infiltration into three consecutive phases: 1) During phase I on days 1 to 2 after allogeneic kidney transplantation, perivascular infiltrates developed that contained numerous donor and recipient macrophages. Allograft rejection could already be diagnosed 24 h after transplantation by perivascular infiltration of T lymphocytes, whereas T cells were rarely found in isografts. 2) Phase II of allograft rejection from day 3 to 4 was characterized by massive propagation of the infiltrate. About equal numbers of interstitial donor and recipient macrophages were counted. Both macrophages and T lymphocytes proliferated in situ and macrophages outnumbered T cells until complete rejection. 3) During phase III the allograft was destroyed. Large intravascular monocytes surprisingly expressed the ED2 antigen. In the interstitium of viable graft regions, the population of recipient macrophages grew, whereas the population of donor macrophages and of T lymphocytes decreased.

Vascular smooth muscle cell (VSMC) migration and proliferation are believed to play key roles in atherosclerosis. To elucidate the role of vascular dopamine D1-like receptors in atherosclerosis, the effects of dopamine and specific D1-like agonists SKF 38,393 and YM 435 on platelet-derived growth factor (PDGF) BB-mediated VSMC migration and proliferation were studied. We observed that cells stimulated by PDGF-BB (5 ng/mL), showed increased migration and proliferation. These effects were prevented by coincubation with dopamine, SKF 38,393, or YM 435 (1 to 10 mumol/L), and this prevention was reversed by Sch 23,390 (1 to 10 mumol/l), a specific D1-like antagonist. These actions are mimicked by forskolin (1 to 10 mumol/L), a direct activator of adenylate cyclase and 8-bromo-cAMP at 0.1 to 1 mmol/L and are blocked by a specific protein kinase A inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H 89), but not blocked by its negative control, N-[2-(N-formyl)-p-chlorociannamylamino)ethyl]-5-isoquinoline sulfonamide (H 85). PDGF-BB (5 ng/mL)-mediated activation of phospholipase D, protein kinase C, and mitogen activated protein kinase activity were significantly suppressed by coincubation with dopamine. These results suggest that vascular D1-like receptor agonists inhibit migration and proliferation of VSMC, possibly through protein kinase A activation and suppression of activated phospholipase D, protein kinase C, and mitogen-activated protein kinase activity.

In order to determine the effects of 1-(2, 6-dimethylphenoxy)-2-(3, 4-dimethoxyphenylethylamino) propane hydrochloride(DDPH) on proliferation of vascular smooth muscle cells(VSMC), growth factor PDGF-B, bFGF and expression of oncogene c-sis and c-myc in spontaneously hypertensive rat(SHR), 3H-thymidine(3H-TdR) incorporation, electronic microscopy, immunohistochemistry and in situ hybridization assays were used. The results showed that after DDPH administration (50 mg i.g. q.d. x8 wk to SHR), morphological change of VSMC was antagonized, blood pressure and 3H-TdR incorporation were significantly reduced. Furthermore, DDPH was shown to reverse the enhanced antigen PDGF-B and bFGF and reverse the reduced expression of oncogene c-sis and c-myc in SHR. These results suggest that DDPH may inhibit VSMC proliferation in SHR, which may be relevant to the molecular biological mechanism of growth factors and oncogene control.

1. Experiments were conducted on cultured renal arterial smooth muscle cells to determine the ability of extracellular ATP to alter cytosolic calcium concentration and to determine the mechanisms by which this effect occurs. 2. ATP (100 mumol/L) caused the fluorescence ratio of fura-2 to increase from a control value of 1.06 +/- 0.05 to 2.06 +/- 0.13 (P < 0.01) before stabilizing at a sustained level of 1.35 +/- 0.04 (n = 8; P < 0.05). 3. Removal of extracellular calcium from the bathing medium resulted in an attenuation of the initial response to 100 mumol/L ATP with cell fluorescence increasing from 1.16 +/- 0.18 to 1.44 +/- 0.18 ratio units (n = 5). Furthermore, the initial increase in fluorescence ratio rapidly declined to 1.02 +/- 0.06, indicating that an influx of extracellular calcium is required to sustain the increase in fura-2 fluorescence. 4. Depletion of intracellular calcium pools with thapsigargin prevented the increase in fura-2 fluorescence evoked by ATP. 5. These data suggest that ATP-mediated increases in cytosolic calcium in cultured renal arterial smooth muscle cells involve calcium release from the thapsigargin-sensitive, intracellular pool in conjunction with calcium influx from the extracellular medium.

It was established macroscopically that 37.5% of the renal veins investigated possess valves. Valves were observed on both sides, but predominantly on the left side of the kidneys (14.58%). Some valves were also observed in the main branches of the renal veins. The structure of the valves was studied with the use of light and electron microscopy. The most important finding was the observation of mast cells in the valves. This is probably a common biological phenomenon, since mast cells have been observed in the cardiac valves and the wall of the renal artery and vein.

The patch-clamp technique was used to examine the inhibition of delayed rectifier K+ channels by agents that release intracellular Ca2+. During voltage-clamp experiments on isolated myocytes with 4-aminopyridine (4-AP, 10 mmol/L) and niflumic acid (100 mumol/L) present to inhibit delayed rectifier K+ current (IK(dr)) and Ca(2+)-activated Cl- current (ICl(Ca)), angiotensin II (Ang II) and caffeine increased Ca(2+)-activated K+ current (IK(Ca)) between -25 and 80 mV (n = 5). Conversely, with charybdotoxin (ChTX, 100 nmol/L) and niflumic acid (100 mumol/L) present to inhibit IK(Ca) and ICl(Ca), Ang II and caffeine only caused inhibition of IK(dr). Block was achieved within 15 seconds of drug application and was reversible upon washout (n = 5). The effects of Ang II on IK(Ca) and IK(dr) were inhibited by the specific Ang II receptor antagonist losartan (1 mmol/L, n = 3). Intracellular BAPTA (10 mmol/L) also abolished the effects of Ang II and caffeine on both IK(Ca) and IK(dr). In current-clamp experiments, the application of ChTX (100 nmol/L) and niflumic acid (100 mumol/L) caused little change in resting membrane potential; however, subsequent application of caffeine (10 mmol/L) caused a 26 +/- 2.9 mV depolarization from -54 +/- 3.1 to -28 +/- 1.7 mV (n = 6). 4-AP (10 mmol/L) blocked the caffeine-induced depolarization. When isolated cells were loaded with the Ca2+ indicator indo 1 (100 mumol/L), Ang II, caffeine, and 4-AP increased [Ca2+]i and depolarized the cells. Both Ang II and caffeine caused an increase in [Ca2+]i that preceded membrane depolarization, whereas 4-AP depolarized the cell first and then caused an increase in [Ca2+]i (n = 4). In inside-out patches, with 200 nmol/L ChTX in the patch pipette to block large-conductance Ca(2+)-activated K+ channels, a 45 +/- 7-picosiemen 4-AP-sensitive K+ channel was identified that was sensitive to cytoplasmic Ca2+ (n = 6). Increasing intracellular Ca2+ decreased channel opening probability [NxP(open), where N is the number of functional channels in a patch and P(open) is the opening probability] at all membrane potentials examined. At 0 mV, increasing Ca2+ from < 5 to 200 and 600 nmol/L free Ca2+ decreased NxP(open) by 52 +/- 3% and 73 +/- 7%, respectively (n = 6). The decrease in opening probability of the delayed rectifier K+ channel resulted from a concentration- and voltage-dependent decrease in mean open time. The decrease in mean open time reflected significant decreases and increases in open and closed time constants, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Male Wistar rats were fed diets containing supplements of either methionine or cystine from 10 weeks of age and compared to rats fed a control diet or a high protein diet kept under identical conditions. At 11-16 months of age, the aorta and the renal, iliac and caudal arteries of all rats were fixed and examined by light and electron microscopy. Cystine-fed rats showed arterial morphology similar to that of control rats and of those having received a high protein diet. Methionine-fed rats showed marked thickening of the arterial wall which was due, on the one hand, to massive intimal thickening, as a result of accumulation of granular material in the subendothelial region and, on the other hand, to marked thickening of the media as a result of increased extracellular material around smooth muscle cells. Zones of early phases of chondroid metaplasia were also observed in the media. Thus cystine and methionine, despite their interrelated metabolism, have very different effects on the morphology of the arterial wall. However, cystine and methionine both inhibited the spontaneous rupture of the internal elastic lamina in the renal artery. This latter result is discussed in the light of the similarities between spontaneous rupture of the internal elastic lamina and beta-aminopropionitrile-induced aortic aneurysm and rupture.

Nitric oxide (NO) release accounts for the biological activity of endothelium-derived relaxing factor. Given that tumor necrosis factor-alpha (TNF-alpha) has been implicated as an important mediator in septic shock, we explored whether TNF-alpha enhances L-arginine-dependent synthesis of NO and L-citrulline in endothelial cells. The release of NO was detected in a coincubation bioassay where measurement of guanosine 3',5'-cyclic monophosphate (cGMP) production in reporter monolayers, namely glomerular mesangial cells or fetal lung fibroblasts, reflected activation of soluble guanylate cyclase. Reporter monolayer cGMP content was greater in the presence of TNF-alpha-treated bovine aortic and renal artery endothelial cells than in the presence of vehicle-treated endothelial cells. TNF-alpha-stimulated endothelium-dependent increases in reporter monolayer cGMP content were first evident at 8 h and maximal at 16-24 h. In addition, TNF-alpha-stimulated endothelium-dependent increases in reporter monolayer cGMP content were abrogated by hemoglobin and methylene blue, blunted by N omega-nitro-L-arginine and augmented by superoxide dismutase and the calcium agonist bradykinin. These observations suggested that TNF-alpha enhanced release of NO. Furthermore, the formation of L-[14C]citrulline from L-[14C]arginine, as determined by quantitative cation-exchange chromatography and thin-layer chromatography, was enhanced by TNF-alpha in a time- and concentration-dependent manner. Thus it is evident that endothelial cells release NO for a prolonged period in response to TNF-alpha and transiently when stimulated with calcium agonists. The prolonged release of NO from TNF-alpha-stimulated endothelial cells may be implicated in the pathogenesis of septic shock.

In this report, we present a three-dimensional computer assisted reconstruction study from serial thin sections through a rabbit renal artery smooth muscle cell. In a series of 32 consecutive thin (100-nm) sections, one longitudinally oriented cell was followed and photographed in alternating sections. The profiles of the cell surface and dense bodies were reconstructed from these 16 planes and the distribution, size, shape, and spatial relationships among these components was examined. The reconstructed images showed that the cell decreases in diameter from its widest region in the center to the two ends in a step-wise taper. Within the cell, dense bodies are numerous. Relative to the cell axes, a membrane associated dense body (MDB) can be less than or equal to 3.5 microns long, 0.25 micron wide, and may extend up to 2 microns in depth. While the MDB profile in one section may be aligned with the long axis of the cell, in an adjacent section the same dense body may appear almost circular or wedge shaped. The same is true of cytoplasmic dense bodies (CDBs). Compared with MDBs, CDBs are smaller in all dimensions. Some, but not all, CDBs line up in strings oriented with the long axis of the cell. The continuity of dense bodies over considerable cell depth and their change in shape may have important implications for integration of contractile activity and for transmitting passive tension to the extracellular matrix.

To evaluate whether intravascular phenomena contribute to local differences in growth responses of the arterial wall, we evaluated responses to organoid culture in a broad variety of arterial preparations. Arterial segments were isolated from adult, normotensive rats, sympathectomized, denuded from endothelium, and suspended in medium supplemented with serum. As judged from the nuclear incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdUrd), this induced a transient stimulation of DNA synthesis in only a fraction of the arterial smooth muscle cells in all types of arteries. This intramedial DNA synthesis was more marked in renal arteries than in carotid arteries or aortae and was least pronounced in main pulmonary, femoral, and superior mesenteric artery and in mesenteric resistance-sized arteries. Organoid culture of isolated arteries did not increase the cross-sectional area of the media or the number of medial cells. It rather resulted in proliferation of smooth-muscle-like cells outside the media. In addition, smooth-muscle-like cells migrated out of the isolated arterial segments during culture. The rate of proliferation of these isolated cells did not differ between large arteries of different anatomical origin. However, isolated cells derived from mesenteric resistance arteries proliferated at a rate that was 4 times slower than that of large artery cells. The presence of endothelium significantly reduced medial DNA synthesis in carotid and renal artery segments, but not in mesenteric resistance-sized preparations. These data indicate that growth responses of the arterial wall differ quantitatively with the anatomical location and branching order of the vascular segment. In addition to the regional heterogeneity of endothelial effects on mitogenic responses of arterial smooth muscle, this seems to be due to regional differences in the susceptibility of arterial smooth muscle to exogenous growth factors. In this respect, we speculate that subsets of growth-resistant and growth-prone arterial smooth muscle cells could be heterogeneously distributed over the arterial tree.

Renal, coeliac and anterior mesenteric arteries from 33 goats of 20 days to over five years of age have been studied. A detailed description of the structure of renal artery of goat, the general histomorphological and histochemical differences in coeliac and anterior mesenteric arteries and the relative extent of age associated changes in them have been discussed.

The effect of glucocorticoids on the dopamine (DA)-mediated cyclic adenosine monophosphate (cAMP) by intact vascular smooth muscle cells (VSMC) was studied in rats. Cultured VSMC were obtained from renal arteries of 14-week-old Wistar-Kyoto rats by explant method. Micromolar concentrations of dexamethasone (DEX) pretreatment for 48 hours potentiated DA-mediated response without any change of affinity constant. However, micromolar concentrations of aldosterone pretreatment for 48 hours had almost no effect on DA-mediated response. The DEX-induced facilitation began at 6 hours and reached maximum at 24 hours after DEX administration in a dose-dependent manner. Inhibitors of protein and RNA synthesis blocked this glucocorticoid effect. The basal activity of adenylate cyclase in DEX-treated cells was twofold higher than that in control cells. Treatment of VSMC with DEX increased cholera toxin-stimulated and forskolin-stimulated adenylate cyclase activity. However, pertussis toxin treatment did not augment or reduce the effect of DEX treatment. These results suggest that glucocorticoids increase DA-mediated cAMP formation by VSMC through glucocorticoid type II receptors and the induction of protein synthesis and that the activation of the catalytic unit may play some role in this facilitation.

The goal of this study was to define some of the cellular and ionic mechanisms of smooth muscle cell activation in dog renal arteries exposed to physiological levels of transmural pressure. Isolated interlobular arteries were cannulated and connected to a pressure reservoir to allow manipulation of transmural pressure in 20-mmHg increment steps from 20 to 120 mmHg. As transmural pressure was increased, vascular smooth muscle exhibited a linear depolarization from an average resting potential of -57 +/- 2 mV at 20 mmHg to -38 +/- 2.4 mV at 120 mmHg. Spontaneous action potentials could often be recorded at pressures greater than 80 mmHg. These appeared to occur primarily at bifurcation points of branching arteries. Vascular smooth muscle depolarization and action potentials occurring in response to increases in transmural pressure were associated with a maintenance of internal diameter of the vessel segments despite increases in transmural pressure in the range between 60 and 120 mmHg. The "pressure-induced" activation of vascular smooth muscle contraction and spontaneous action potentials of small renal arteries at higher transmural pressures were blocked on Ca2+ channel inhibition with verapamil (10(-6) M). These data document a membrane ionic mechanism (probably increased Ca2+ influx) for pressure-induced myogenic activation of isolated renal arteries. It is interesting that the contraction of these vessels occurs over the pressure range in which autoregulation of renal blood flow normally occurs. The physiological significance of these responses needs to be determined.

The availability of specific antisera to renin and the techniques of immunocytochemistry have facilitated the microscope study of renin-secreting cells. These techniques have been used in recent studies in the developing kidney as well as in both normal and pathological adult kidney. This work has clarified the close relationship between myoepithelioid cell and the blood vessel. The use of ultrastructural immunocytochemistry has led to new insights into the intracellular processing, storage and secretion of renin. These recent morphological studies are reviewed with the emphasis on the human renin-secreting cell within the kidney.

An increasing body of evidence implies that the results of pharmacological studies of blood vessels may depend on the presence of an intact layer of endothelial cells inside the blood vessels. This is often inadvertently removed during the early part of the experiment and it is thus necessary to have some means of determining whether the endothelium is intact or has suffered extensive damage. Previous reports describe a stain that will enable the endothelial cells to be visualized, however we find that in the cerebral vasculature this approach is unsatisfactory in that it provides a gross underestimate of the amount of intact endothelium. A modification of the original procedure is described that provides results that correspond well with those of scanning or transmission electron microscopy.

Verhoeff (1908) recommended an iron-hematein formula containing Lugol's solution for demonstration of elastic tissue; sections are differentiated until desired staining patterns are obtained. Verhoeff's stain colored a variety of tissue structures and showed higher substantivity for myelin sheaths than for elastin. Addition of HCL or omission of Lugol's solution decreased or abolished coloration of pseudo-elastica and thus enhanced selectivity for elastin. Substitution of Fe++ for Fe+++ abolished dye binding by elastin. A review of chemical data indicated interaction of components of Lugol's solution with the dye. Hematein and Fe+++ form a variety of cationic, anionic and non-ionic chelates; the ratio of these compounds changes with time. Dye binding apparently occurs mainly via van der Waals forces and hydrogen bonds. Verhoeff's elastica stain is definitely not specific for elastin and is inferior to orcein and resorcin-fuchsin because of the required differentiation with its inherent bias to produce patterns which conform to expectations. However, Verhoeff's elastica stain is far superior to other metal-hematein technics for myelin sheaths. The combined Verhoeff-picro-Sirius Red F3BA stain can be performed in 30 min and does not require differentiation. It is therefore suggested to reclassify Verhoeff's elastica stain as a method for myelin sheaths.

Aortorenal interposition grafts were performed in dogs using a new external velour knitted Dacron graft. Encapsulation and endothelialization of these grafts occurs as early as two weeks postoperatively. Complete healing is seen by six weeks, and the cellular lining of these grafts appears to be continuous with, and histologically similar to, the endothelium of contiguous arteries. The healed nonthrombogenic characteristics of this graft material represents a considerable improvement over graft materials of conventional design.

Original Gianturco steel coil vascular embolization devices and two modifications were compared for their occlusive effects and for the degree of adverse reaction in the surrounding vessel wall. Modifications consisted of silk or Ivalon replacing the wool strands of the original device. Single coils were placed into the left renal artery of nine mixed breed swine and restudied 3 months later. The bare coils did not occlude the vessels nor lead to significant foreign body reaction. Wool, silk, and Ivalon coils produced prompt and sustained renal artery occlusion. Upon histologic examination of the vessel wall, foreign body and chronic inflammatory reaction was found to be strongest against wool. This reaction was less with silk and markedly diminished with Ivalon. The results indicate that silk and Ivalon coils, while having the same occlusive effect, are preferable to wool coils if less local reaction is desired.

The arrangement and structure of renal blood vessels were studied in a marine skate with injection of silicone rubber and methacrylate resin after intravenous administration of epinephrine and perfusion fixation. The methacrylate casts were investigated with the scanning electron microscope. Histology was performed by light and transmission electron microscopy of serial sections. The course of the blood vessels is described in relation to the renal zones of lateral bundles and mesial tissue. Each nephron performs two loops in the lateral bundles and two coilings in the mesial tissue before it joins the collecting duct system. The lateral bundles contain an elaborate countercurrent arrangement of neck segment, proximal tubule segment PIa, early distal tubule segment, and collecting tubule. Within the bundles, the nephron portions are associated with a blind-ended central vessel, which is connected with the venous sinuses of the mesial tissue. The microcirculatory bed around the bundles is supplied with arterial blood via small bundle arteries that originate from the intrarenal arteries in parallel to the afferent arterioles of the glomeruli. The efferent arterioles of the glomeruli convey their blood to the peritubular sinuses of the mesial tissue, which is largely irrigated with venous blood of the renal portal system. The mesial tissue, containing the proximal tubule segments PIb and PII, intermediate segment, and late distal tubule segment LDTb, receives venous blood from the caudal vein and the lateral musculature via afferent renal and intrarenal veins and from the efferent arterioles of the glomeruli and venules of the microcirculation of the bundles. The sinuses are drained by efferent renal veins via efferent intrarenal veins. By comparing the renal structures of the skate with those of dogfish, a unique type of circulation--as related to nephron segments, renal zones, and fine structure of the wall of the vessels--is revealed in marine elasmobranchs of different evolutionary levels.