Long-term studies of the juxtaglomerular apparatus in young microalbuminuric type 1 diabetic patients

AIM: To determine the long-term changes of the juxtaglomerular apparatus in incipient diabetic nephropathy. METHODS: Three renal needle biopsies were performed on 15 young type I diabetic patients with microalbuminuria; at baseline and after an average of 2.4 and 8.2 years. Using light microscopy, 1 microm serial sections of the plastic-embedded biopsies were investigated and volumes of the juxtaglomerular apparatus and glomerulus and areas of the macula densa and lumina of the afferent and efferent arterioles were measured. RESULTS: From baseline to second follow-up there was a significant decrease in JGA relative to glomerular volume. There was an increase in luminal area of the efferent arteriole which was paralleled by (non-significant) changes in the afferent arteriole. CONCLUSION: Over a period of 8.2 years JGA size remained stable, but decreased relative to glomerular size. Also, an increase in luminal area was noted in efferent arterioles. This may be due to increased single nephron blood flow secondary to nephron loss.     

Quantitative ultrastructural study of afferent and efferent arterioles in IgA glomerulonephritis and benign nephrosclerosis

Arteriolosclerosis frequently occurs in IgA nephritis (IgAN), and it is the hallmark of benign nephrosclerosis (BNS). The quantitative ultrastructure of juxtaglomerular arterioles is not known in these disorders. We examined afferent and efferent arterioles in renal biopsies from 25 adult patients with IgAN (hypertension at biopsy: 14 patients) and 9 patients with BNS. Six agematched living renal transplant donors acted as controls. A systematic independent sample of profiles was obtained in thin sections taken at predetermined levels. The thickness of the media (myomedial cells plus the matrix) and the thickness of the medial matrix were estimated stereologically. From these estimates, the matrix/myomedia ratio was calculated. In IgAN with normotension or hypertension, the afferent media and its compartments did not exhibit significant thickening compared with the controls, whereas in BNS the afferent media and its layers were markedly and significantly thickened. The efferent media in IgAN and BNS displayed mild and significant thickening, with significant thickening of the matrix in BNS and IgAN with normotension. The matrix/myomedia ratio was not altered significantly in any group. The results indicate that the afferent arterioles are not the main sites of IgAN-related arteriolosclerosis, that arteriolosclerosis in IgAN and arteriolosclerosis in BNS are different lesions, and that increased efferent arteriolar thickness, demonstrated here for the first time in IgAN and BNS, might be a manifestation of angiotensin II-mediated autoregulatory efferent vasoconstriction exerted to maintain the glomerular filtration pressure.     

The juxtaglomerular apparatus in young type-1 diabetic patients with microalbuminuria. Effect of antihypertensive treatment

BACKGROUND: Our goal was to investigate the effect of antihypertensive drugs on the juxtaglomerular apparatus (JGA) in young type-1 diabetic patients with microalbuminuria. METHODS: Twelve patients were allocated to treatment with either an angiotensin-converting enzyme inhibitor (group 1, six subjects) or a beta-receptor blocker (group 2, six subjects). A comparable group of nine patients without antihypertensive treatment provided reference values (group 3, nine subjects). Renal biopsies were taken at baseline and after a median of 40 months (groups 1 and 2) and 30 months (group 3). Using light microscopy with 1microm serial sections of the plastic-embedded biopsies, volumes of the JGA and glomerulus and areas of the macula densa and lumina of the afferent and efferent arterioles were obtained. RESULTS: A significant decrease of the volume of the JGA (P=0.026) and of the volume of the JGA relative to that of its corresponding glomerulus (P=0.0005) was noted in the reference group only. Negative correlations existed between the increase in the luminal area of the afferent arteriole and mean diastolic blood pressure in the study period in group 1 (P=0.024) and group 2 (P=0.032). CONCLUSIONS: Our results showed that a decrease in the size of the JGA is offset by antihypertensives. The negative correlation between the change in the luminal area of the afferent arteriole and mean diastolic blood pressure in groups 1 and 2 suggest that renal protection in antihypertensive treatment may be through a better constriction of the afferent arteriole protecting the glomerulus from systemic blood pressure.     

Increased eNOS accounts for changes in connexin expression in renal arterioles during diabetes

Previous studies have shown that connexin (Cx) expression is considerably higher in the preglomerular compared to postglomerular vasculature and that these differences are accentuated during diabetes. Since nitric oxide (NO) has been reported to alter Cx expression in endothelial cells and muscle cells and NO bioavailability is altered in diabetes, we hypothesized that NO may be responsible for the changes during diabetes. Cx expression was studied using immunohistochemistry in mice in which eNOS expression was either upregulated (eNOS transgenic) or downregulated (eNOS knockout). Diabetes was induced intraperitoneally with a single dose of alloxan or multiple low doses of streptozotocin. Expression of Cx40 in smooth muscle cells of afferent arterioles was increased, while expression of Cx43 in endothelial cells of efferent arterioles was absent in eNOS transgenic mice, similar to the changes occurring in wild-type mice during diabetes. Expression of Cx40 and Cx43 in eNOS knockout mice was not different from control; however, induction of diabetes in eNOS knockout mice failed to produce any changes in Cx40 or Cx43 in either afferent or efferent arterioles. Immunohistochemistry showed that eNOS expression was increased in the endothelium of renal arterioles in wild-type diabetic and eNOS transgenic mice, but absent from arterioles of eNOS knockout mice. We conclude that changes occurring in Cx expression in afferent and efferent arterioles during diabetes may result from increased eNOS.     

IgA肾病中肾小动脉增厚及其临床评价

目的:目的观测IgA肾病肾小动脉病理学改变,探讨小动脉增厚与临床症状及病理学改变的关系.方法:选内蒙古地区汉族110例IgA肾病患者,医学图像分析系统单盲法测算小动脉血管腔内径与血管外径比值,分析小动脉增厚与临床症状及病理学改变的关系.结果:①IgA肾病小动脉增厚可表现为肌层增厚或玻璃样变性,造成管腔狭窄,两者可共存....     

Renal corpuscular hydrodynamics: Digital computer simulation

Summary A mathematical model of the renal corpuscle is presented and used to quantify the effect on filtration rate, nephron blood flow and hydrostatic pressure in the glomerular capillaries of variations in: 1. the hydrostatic pressure in Bowman's space; 2. the hydrodynamic resistances of the afferent and efferent arterioles; 3. the ultrafiltration coefficient of the glomerular membrane; 4. the hydrostatic pressure in the peritubular capillaries; 5. the arterial haematocrit and plasma protein concentration. The model is derived from the principle of conservation of mass and volume. Hydrostatic pressure gradients along the glomerular capillaries are neglectec. The hydrodynamic resistances of the afferent and efferent arterioles are assumed to be determined by two independent factors, one being determined by the vascular dimensions, the other by the haematocrit. Blood flow is considered to be related in a linear manner to the hydrostatic pressure decreases along these vessels. The effect of changing the hydrostatic pressure in Bowman's space on nephronGFR was calculated and found to agree with experimental measurements. When corpuscular hydrodynamics are related to variations in the hydrodynamic resistance of the afferent or efferent arteriole it is seen that the change in efferent arteriolar plasma flow accompanying altered nephronGFR is very sensitive to the way in which the change is produced. In contrast changes in glomerular capillary pressure and filtration fraction are insensitive. The calculations indicate that differences measured in nephronGFR between superficial and juxtamedullary nephrons can be explained by assuming that the diameters of the afferent and efferent arterioles of the juxtamedullary nephrons increase in direct proportion to the diameter of the renal corpuscle.     

The juxtaglomerular apparatus in IgA nephropathy: An analysis of the transport and fate of IgA deposits at the glomerular hilus

Summary This study on 27 cases of IgA nephropathy has shown that IgA deposits are rare in the juxtaglomerular apparatus (JGA) despite large amounts of IgA deposits in the mesangium. Phagocytes are absent in JGA. A small number of ill-defined, IgA-positive substances are seen in the matrix of lacis cells, and their electron-density is decreased. These findings indicate dissolution of IgA deposits in the intercellular matrix. In addition, it is suggested that the transport of IgA deposits through the glomerular stalk toward JGA is prevented at the border area between the mesangium of glomerular hilus and the lacis cell region. The block is not complete, because small, IgA-positive substances are seen sparsely in the matrix of lacis cells. The structure of the lacis cell region is thought to restrict the passage of macromolecules such as IgA deposits. Frequently positive staining for C3 in the mesangium and lacis cell region and within the wall of afferent and efferent arterioles indicates that C3 is easily accessible to the arteriolar wall adjacent to JGA, by the route through the glomerular stalk and JGA. This may be concerned in the pathogenesis of arteriolar hyalinosis at the glomerular hilus.     

Scanning electron microscopy studies of the vascular pole of the rat glomerulus

The vascular poles of 30 renal corpuscles were studied in critical-point dried renal cortex of the Munich-Wistar rat by scanning electron microscope (SEM). In 28 cases one afferent and one efferent arteriole were observed; one afferent and two efferent arterioles were found in two cases only. The same study was done in the Sprague-Dawley rat, where 34 renal corpuscles were examined. One afferent and a single efferent arteriole were found in 32 cases; in one case only one afferent and two efferent arterioles were observed. In another case it was questioned whether a single or a double efferent arteriole arteriole is present. In addition, the specimens allowed an evaluation of the area where the extraglomerular mesangium passes into the mesangial cells of the glomerular tuft. This area was found to be rather small to represent a “punctum fixum” for a contraction of the entire mesangium.     

Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy

BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal disease. Interruption of the renin-angiotensin system slows the progression of renal disease in patients with type 1 diabetes, but similar data are not available for patients with type 2, the most common form of diabetes. We assessed the role of the angiotensin-II-receptor antagonist losartan in patients with type 2 diabetes and nephropathy. METHODS: A total of 1513 patients were enrolled in this randomized, double-blind study comparing losartan (50 to 100 mg once daily) with placebo, both taken in addition to conventional antihypertensive treatment (calcium-channel antagonists, diuretics, alpha-blockers, beta-blockers, and centrally acting agents), for a mean of 3.4 years. The primary outcome was the composite of a doubling of the base-line serum creatinine concentration, end-stage renal disease, or death. Secondary end points included a composite of morbidity and mortality from cardiovascular causes, proteinuria, and the rate of progression of renal disease. RESULTS: A total of 327 patients in the losartan group reached the primary end point, as compared with 359 in the placebo group (risk reduction, 16 percent; P=0.02). Losartan reduced the incidence of a doubling of the serum creatinine concentration (risk reduction, 25 percent; P=0.006) and end-stage renal disease (risk reduction, 28 percent; P=0.002) but had no effect on the rate of death. The benefit exceeded that attributable to changes in blood pressure. The composite of morbidity and mortality from cardiovascular causes was similar in the two groups, although the rate of first hospitalization for heart failure was significantly lower with losartan (risk reduction, 32 percent; P=0.005). The level of proteinuria declined by 35 percent with losartan (P<0.001 for the comparison with placebo). CONCLUSIONS: Losartan conferred significant renal benefits in patients with type 2 diabetes and nephropathy, and it was generally well tolerated.     

Renal microvasculature of the rainbow trout, Salmo gairdneri: scanning electron microscopy of corrosion casts of glomeruli

Scanning electron microscopy of corrosion casts of blood vessels permits detailed and accurate study of the microcirculation. The present study examined the renal microvasculature of the rainbow trout, Salmo gairdneri. The conventional picture of a glomerulus with one afferent arteriole was common, but glomeruli were often supplied by two afferent arterioles. In the majority of these, the intrarenal artery gave rise to a single afferent arteriole that branched to form two smaller vessels before reaching the glomerulus. Glomeruli with two afferent arterioles that arose independently from the intrarenal artery also occurred. The majority of glomeruli had a single efferent arteriole, but a proportion of glomeruli had two efferent arterioles. Efferent arterioles were smaller in diameter than the afferent arterioles. The glomerular capillaries were arranged in lobules, with few anastomoses between lobules, so that, for glomeruli with two afferent or two efferent arterioles, vascular perfusion and thus filtration within discrete lobules is probable.     

Interstitial capillary changes in lithium nephropathy: effects of antihypertensive treatment

Histopathological changes were investigated in the tubulointerstitium and in the capillaries of male Wistar rats with lithium-induced nephropathy using stereological methods. Two antihypertensive drugs with opposite effects on the renin-angiotensin system, an ACE inhibitor (angiotensin converting enzyme inhibitor) and a thiazide diuretic, modified the nephropathy. Generally, there was a significant positive correlation between the reduction in GFR (glomerular filtration rate) and the reduction in the volume of intact tubular structures and interstitial capillaries. A significant negative correlation was seen between the reduction in GFR and the increase in tubulocapillary distance and the absolute volume of interstitial connective tissue, respectively. Treatment with perindopril, and to some extent hydrochlorothiazide, reversed the rise in systolic blood pressure associated with lithium-induced nephropathy but did not affect the progression to terminal uraemia, the structural renal changes or the mortality. In conclusion, severe tubular and capillary changes are seen in this model of chronic renal failure. Tubular atrophy is associated with a decrease in interstitial capillaries and with an increase in the tubulocapillary distance. Systemic hypertension or activation of the renin-angiotensin system may not be important factors for the progression to terminal renal failure.     

Morphometric analysis of arteriolar diameters in experimental nephropathies: Application of microvascular casts

Summary Renal arteriolar diameters were measured, using microvascular resin casts, in two hyperfiltration models of rats: the remnants kidney of subtotal nephrectomy (NX) and streptozotocin-induced diabetic kidney (DM). In the NX, the blood pressure was elevated, urinary protein excretion was markedly increased and glomeruli were severely damaged. In the DM, although the blood pressure remained normal, urinary protein excretion was significantly increased and glomeruli were damaged but to a lesser extent than in the NX group. In the NX group, the afferent arteriole was dilated and the efferent arteriole was constricted. In the DM group, the afferent arteriole was dilated, while the efferent arteriole remained unchanged. The results showed that afferent arteriolar dilatation was seen in both the NX and DM groups, possibly leading to the glomerular damage. In the NX group, the systemic high blood pressure and efferent arteriolar constriction augmented glomerular damage significantly.     

中美两种2型糖尿病肾病诊断标准中疾病进展及预后因素对比

目的 通过对美国肾脏病基金会肾脏病预后质量倡议（NKF K/DOQI）标准及中华医学会糖尿病学分会微血管并发症学组的标准所描述的2型糖尿病肾病疾病进展及预后因素进行对比,评估两种标准的临床应用价值。方法 选取2016年4月~2017年4月于佛山市第二人民医院就诊的2型糖尿病患者共280例作研究对象,其中符合NKF K/DOQI标准的2型糖尿病肾病患者70例,符合中华医学会标准者80例。记录两种标准2型糖尿病肾病患者的肾小球滤过率,两组患者接受1年回访后对上述指标进行复查,统计两种标准患者的肾功能进展性下降的比例并进行对比。使用Spearson法分析eGFR下降幅度与各可能危险因素的相关性,使用Logistic回归模型分析随访后eGFR下降与各可能危险因素的相关性。结果 中华医学会标准诊断2型糖尿病患者的糖尿病肾病患病率为:28.57%（80/280）;NKF K/DOQI标准诊断2型糖尿病患者的糖尿病肾病患病率为25.00%（70/280）;按中华医学会标准,正常白蛋白尿的2型糖尿病肾病患者占2型糖尿病肾病患者的12.50%（10/80）;两种标准下,糖尿病肾病患者出现eGFR降低≥4%/年的比例均高于非糖尿病肾病者,中华医学会标准组为:20.00% vs 9.00%（P＜0.05）;NKF K/DOQI标准组为:17.14% vs 6.67%（P＜0.05）;两种标准下糖尿病肾病与非糖尿病肾病在eGFR降低＜4%及eGFR无下降的患者比较,差异无统计学意义（P＞0.05）;Logistic回归分析中,校正年龄、血糖、病程等危险因素后,中华医学会标准下糖尿病病程≥10年、HbA1C、基线eGFR与eGFR进展性下降存在显著相关性;NKF K/DOQI标准下糖尿病病程≥10年、高血压、HbA1C、基线eGFR、糖尿病视网膜病变与eGFR进展性下降存在显著相关性。结论 两种标准诊断的糖尿病肾病患者肾功能进展性下降程度均高于非糖尿病肾病患者,预测两种标准糖尿病肾病发生肾功能进展性下降的基线预后因素相似,本研究对中华医学会标准将正常白蛋白尿但eGFR下降的临床亚型归入2型糖尿病肾病诊断范畴的建议提供了流行病学的间接证据。     

Role of macula densa neuronal nitric oxide synthase in renal diseases

Macula densa cells have an important role in the regulation of glomerular blood flow and glomerular filtration by its regulation of afferent arteriolar vascular tone. Nitric oxide derived from neuronal nitric oxide synthase (nNOS) in macula densa can dilate afferent arterioles. Macula densa nNOS is important for renin secretion, and its expression is regulated by dietary salt, renal angiotensin II, intracellular pH, and other factors. In salt-sensitive hypertension, nNOS is suppressed, whereas in SHR or in the early phase of diabetes, nNOS is increased in macula densa along with NADPH oxidase, which limits NO bioavailability. Renal damage induced by hypertension, diabetes, and hyperlipidemia could be prevented by enhancement of nNOS in macula densa with ACEI, dipyridamole, α₁-receptor blocker, a low-salt diet, or sodium bicarbonate. Sodium bicarbonate is a safe and clinically available enhancer of nNOS in macula densa that increases glomerular blood flow and prevents the reduction of GFR in radiocontrast nephropathy and chronic renal failure. In conclusion, the enhancement of nNOS in the macula densa can be a promising strategy to prevent reduction of renal function.     

Uridine adenosine tetraphosphate acts as an autocrine hormone affecting glomerular filtration rate

Recently, uridine adenosine tetraphosphate (Up(4)A) was described as a strong vasoconstrictor released from endothelial cells after stimulation with mechanical stress. In this study, we isolated and identified Up(4)A from kidney tissue, and we characterized the essential varying effects of Up(4)A on the afferent and efferent arterioles. Porcine and human kidney tissue was fractionated by size exclusion chromatography, affinity chromatography, anion exchange chromatography and reverse phase chromatography. In fractions purified to homogeneity, Up(4)A was identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS), MALDI-LIFT fragment mass spectrometry (MALDI-TOF/TOF MS), retention-time comparison and enzymatic cleavage analysis. We analysed the release of Up(4)A from cultivated renal proximal tubule cells after stimulation of protein kinase C with oleoyl-2-acetyl-sn-glycerol (OAG). Up(4)A was identified in renal tissue, and the effect of Up(4)A on the vascular tone of isolated perfused afferent and efferent arterioles was tested. Stimulation of tubule cells with OAG increased the release rate of Up(4)A from tubule cells about tenfold. Up(4)A acts as a strong vasoconstrictive mediator on afferent arterioles, but has no significant effect on the tone of efferent arterioles, suggesting a functional role of Up(4)A as an autocrine hormone for glomerular perfusion. Because of the predominant effect of the Up(4)A on afferent arterioles, we assume that Up(4)A may decrease glomerular perfusion, intra-glomerular pressure and, hence, glomerular filtration rate. The release of Up(4)A from renal tubular cells may be an additional mechanism whereby tubular cells could affect renal perfusion. Up(4)A release may further contribute to renal vascular autoregulation mechanisms. In conclusion, as Up(4)A occurs in renal tissue and has marked effects on afferent but not efferent arterioles, Up(4)A may play a role in renal hemodynamics and possibly blood pressure regulation.     

Percutaneous Renal Sympathetic Denervation for the Treatment of Resistant Hypertension with Heart Failure: First Experience in Korea

Percutaneous catheter-based therapy has recently been introduced to decrease blood pressure by ablation of efferent and afferent sympathetic renal nerves. The patient described here had a seven-year history of hypertension and presented with poorly controlled blood pressure despite antihypertensive therapy with four different drugs. A 44-yr-old man underwent percutaneous renal denervation under local anesthesia using an ablation catheter. After six months of follow-up his blood pressure had dropped 49/37 mmHg with a decrease in 24-hr ambulatory BP of 20/18 mmHg. Renal Doppler ultrasound showed no significant stenosis in either renal artery. This is the first case of successful percutaneous renal denervation, which has recently become available in Korea.     

Renal Involvement in the Antiphospholipid Syndrome (APS)—APS Nephropathy

Although the kidney represents a major target organ in antiphospholipid syndrome (APS), renal involvement in APS was poorly recognized until recently. The most well-recognized renal manifestations of APS are the renal artery thrombosis/stenosis, renal infarction, hypertension, renal vein thrombosis, end-stage renal disease, increased allograft vascular thrombosis, some types of glomerular disease, and a small-vessel vaso-occlusive nephropathy, recently defined as APS nephropathy. APS nephropathy was first described in primary APS patients, characterized by acute thrombotic lesions in glomeruli and/or arterioles (thrombotic microangiopathy) and chronic vascular lesions such as fibrous intimal hyperplasia of arterioles and interlobular arteries, organized thrombi with or without recanalization, and fibrous arterial and arteriolar occlusions or focal cortical atrophy. APS nephropathy was also detected in further studies including patients with systemic lupus erythematosus (SLE)-related APS and SLE/non-APS patients with positive antiphospholipid antibodies, independently of lupus nephritis. The same histologic lesions, especially thrombotic mictroangiopathy, were also observed in patients with catastrophic APS. The most frequent clinical and laboratory characteristics of APS nephropathy in all the above groups of patients are hypertension (often severe), proteinuria (ranging from mild to nephrotic range), hematuria, and acute or chronic renal insufficiency.     

Variations in arterioles in spontaneously hypertensive rats

Summary In the present study, the diameters of afferent and efferent arterioles of kidneys from spontaneously hypertensive rats (SHR) were evaluated and compared with those from Wistar Kyoto rats (WKY) using a vascular cast model. At 4 weeks of age, the blood pressure was slightly higher in SHR than in WKY (124±1 vs 116±7 mmHg, ns). The diameters of afferent arterioles in SHR were smaller than those in WKY (10.3±0.6 vs 12.3±0.7 µm,P<0.001), whereas the diameters of efferent arterioles were comparable in the two strains. At 20 weeks of age, the blood pressure was markedly elevated in SHR than in WKY (192±5 vs 140±4 mmHg,P<0.001). The diameters of afferent arterioles in SHR at this age were much smaller than those in WKY (14.3±0.5 vs 17.1±0.6 µm,P<0.01). The diameters of efferent arterioles in SHR were, however, larger than those in WKY (15.4±l.2 vs 12.9±0.4 µm,P< 0.05). The net effect of these changes in arteriolar size helps to maintain normal intraglomerular pressure and to protect glomeruli from damage due to hypertension.     

Three-dimensional analysis of increased vasculature around the glomerular vascular pole in diabetic nephropathy

In diabetic nephropathy, several small vessels are frequently observed around the glomerular vascular pole in addition to the usual afferent and efferent arterioles. To elucidate the morphology of these abnormal small vessels, a three-dimensional study was performed by using computer-aided reconstruction techniques. In the present study, the renal tissue samples of 21 biopsy and 73 autopsy cases of diabetic glomerulonephropathy were examined. In addition to ordinary light microscopic observations, three series of serial sections from one autopsy and two biopsy cases were analysed. Five glomeruli with increased numbers of vessels around the vascular pole were reconstructed three-dimensionally. The vasculature in and around the glomerulus was analysed in detail by rotating and viewing in different planes via computer-generated three-dimensional images. These vessels anastomose to the lobular structure of the intraglomerular capillary network, mainly to the afferent branches through the widened vascular hilus. The distal end of the vessels anastomoses to the peritubular capillary. The increased vasculature is interpreted as neoangiogenesis resulting from diabetes, which may have a functional role in facilitating efferent blood flow from the glomerulus.Dr. Wen Min is a visiting research fellow from Norman Bethune University of Medical Sciences, China     

Relationship between PGE2 and renin release in dog kidneys. Effects of afferent arteriolar dilation and adrenergic stimulation

To study the relationship between PGE2 and renin release from the kidney, examinations were performed on anesthetized dogs during afferent arteriolar dilation. This condition is known to increase renin release and enhance the stimulatory effects on renin release of beta-adrenergic agonists, such as isoproterenol. Afferent arteriolar dilation induced by constricting the renal artery or occluding the ureter increased PGE2 and renin release before, but not after, indomethacin administration. Isoproterenol infusion during afferent arteriolar dilation increased renin release but not PGE2 release both before and after indomethacin administration. Phenylephrine, an alpha-adrenergic agonist, which also induces afferent arteriolar dilation, increased PGE2 and renin release at control blood pressure but not when the afferent arterioles already were dilated by ureteral occlusion. We conclude that afferent arteriolar dilation caused by renal arterial constriction, ureteral occlusion or infusion of phenylephrine increases prostaglandin synthesis which stimulates renin release. The effect of isoproterenol on renin release is independent of prostaglandin synthesis.