Neural control of renal hemodynamics and function during development

This review summarizes our current understanding of the role of the renal sympathetic nervous system during development. Recent evidence suggests that renal innervation appears early during fetal life and may play an important role in promoting cellular development. It has also been observed that renal nerve stimulation decreases renal blood flow and increases renal vascular resistance in fetal sheep, but to a lesser extent than in newborn and adult sheep. Moreover, it has been shown that, contrary to previous findings in adult animals, renal nerve stimulation during -adrenoceptor blockade induces renal vasodilation in fetal and newborn sheep, but not in adult sheep. Recent studies have also demonstrated that renal nerves modulate the natriuretic response to a saline load in newborn lambs and influence sodium reabsorption in near-term fetal sheep. The role of renal nerves and neuronally released norepinephrine on renin secretion in the developing kidney is discussed. Finally, it is suggested that efferent renal sympathetic nerve activity might influence fetal renal hemodynamics during stressful conditions.     

The renal nerves in the newborn rat

Immunocytochemical methods were used to investigate the distribution of afferent [calcitonin gene-related peptide-(CGRP) immunoreactive and substance P-immunoreactive] nerves and efferent (neuropeptide Y-immunoreactive and dopamine -hydroxylase-immunoreactive) nerves in the kidneys of rats within the 1st day of life. The newborn rat kidney possesses an afferent and efferent innervation. Both afferent and efferent nerves reach the kidney in the same bundles. The afferent sensory fibers predominate overwhelmingly in the renal pelvis and ureter while the efferent fibers clearly predominate in the vasculature. The corticomedullary connective tissue contains both types of innervation with a more prominent afferent innervation (CGRP immunoreactive). Only afferent arterioles of perihilar nephrons were innervated by efferent sympathetic fibers. The distribution and extent of afferent and efferent innervation is consistent with the renal nerves playing a significant role in the transition from fetal to newborn life. The close proximity between afferent and efferent fibers suggests a possible interaction between the two systems.     

Mechanisms regulating renal sodium excretion during development

The present review focuses on the ontogeny of mechanisms involved in renal sodium excretion during renal maturation. The effect of birth on renal excretion of sodium and the role played by the different tubular segments in the regulation of sodium excretion during maturation are discussed. The influence of circulating catecholamines and renal sympathetic innervation in regulating sodium excretion during renal development is reviewed. The effects of aldosterone, atrial natriuretic factor, and prostaglandins on sodium regulation during renal maturation are discussed. Special emphasis is given to the potential role of glucocorticoids in modulating sodium excretion early in life.     

Clinical and experimental study of the production of renal hemodynamic effects of IABP-assisted pulsatile flow extracorporeal circulation]

Renal hemodynamics during IABP-assisted pulsatile flow extracorporeal circulation was assessed in terms of measurement values for intraoperative renal blood flow obtained by the local thermodilution method in human clinical patients. In addition, the effect of IABP on renal hemodynamics was investigated in an animal model of renal denervation in a study undertaken to elucidate the action mechanism of IABP. Eighteen patients with acquired heart disease were involved in the study and measured for the renal blood flow (RBF), cardiac output (CO), renal-systemic partition coefficient for blood flow (RBF/CO), renal vascular resistance (RVR) and perfusion pressure. In the pulsatile flow group, the RBF/CO increased as the number of pump runs increased, whole the RVR was conversely reduced with increasing pump runs. The experimental study without extracorporeal circulation was conducted on 19 mongrel dogs. During IABP runs RBF/CO increased, while the RVR decreased. After renal denervation, no noticeable influence of IABP upon renal hemodynamics was observed. Following a loading dose of noradrenaline (Norad), the RVR increased in a Norad concentration-dependent fashion, independently of IABP and renal denervation. These results indicate that IABP reduces the RVR and thereby exerts a favorable action on renal hemodynamics during pump times. The study thus warrants us to surmise that a mechanism involving the renal sympathetic nerves might play an important role in the production of favorable renal hemodynamic effects of IABP-assisted pulsatile flow extracorporeal circulation.     

The kidney in the pathogenesis of hypertension: the role of renal nerves

The intrinsic efferent innervation of the kidney consists of exclusively noradrenergic fibers that innervate the preglomerular and postgomerular vasculature, all elements of the juxtagomerular apparatus and virtually all segments of the nephron in both cortical and medullo-papillary regions. Increases in efferent renal sympathetic nerve activity produce renal vasoconstriction, release of renin, catecholamines, prostaglandins and other vasoactive substances, and increases in renal tubular sodium reabsorption; these responses are graded and differentiated. The intrinsic afferent innervation of the kidney consists of mechanoreceptors and chemoreceptors which participate in reno-renal and reno-systemic reflexes that modulate sympathetic neural outflow in an organ-specific differentiated pattern. Therefore, alterations in efferent and afferent renal nerve activity produce changes in several important renal functions known to contribute to the development and maintenance of hypertension.     

Severe hypertension and massive proteinuria in a newborn with renal artery stenosis

Renal vein thrombosis and the congenital nephrotic syndrome have been associated with nephrotic-range proteinuria/nephrotic syndrome and hypertension in the newborn period. We describe a newborn with severe hypertension and proteinuria secondary to unilateral renal artery stenosis. Proteinuria completely disappeared with blood pressure control (with sodium nitroprusside and an angiotensin-converting enzyme inhibitor). Although renin was not measured, we speculate that proteinuria might have been induced by a high renin state, and was controlled by the angiotensin-converting enzyme inhibitor.     

Bradykinin and hypoxemia-induced renal changes in the newborn rabbit

Acute hypoxemia causes a decrease in glomerular filtration rate (GFR) and renal blood flow (RBF) in newborns. These changes are partly mediated by local-acting vasoactive factors. We have previously shown that bradykinin (BK) has a vasodilatory role in the basic regulation of neonatal hemodynamics. The purpose of the present study was to evaluate whether BK can modulate the severe renal vasoconstriction associated with hypoxemia in the newborn rabbit. The effect of systemic hypoxemia (PaO₂ approximately 40 mmHg) on renal function was investigated in 9 newborn rabbits (controls) and in 8 animals in which BK-B2 receptors were blocked by Hoe 140 (300 μg/kg subcutaneously), given prior to the induction of hypoxemia. The studies were performed under pentobarbital anesthesia at the age of 5 – 9 days. In control animals, acute hypoxemia caused a significant decrease in GFR and RBF and an increase in renal vascular resistance. Similar glomerular hemodynamic changes were observed in BK-B2 receptor-blocked newborn rabbits. These results indicate that BK does not play a significant role in the renal vascular changes of the hypoxemic-stressed newborn. Received June 6, 1997; received in revised form November 14, 1997; accepted November 19, 1997     

The salt paradox of the early diabetic kidney is independent of renal innervation

Glomerular filtration rate (GFR) is inversely and thus paradoxically related to dietary NaCl intake in rats and patients with early type 1 diabetes mellitus (DM). Enhanced sensitivity of proximal reabsorption to NaCl diet inducing secondary adaptations in GFR through actions of tubuloglomerular feedback causes this salt paradox. We studied the role of renal nerves for the salt paradox in rats with streptozotocin (STZ)-induced DM since a regulatory influence of renal nerves on proximal reabsorption is well established. The left kidney (LK) was denervated before induction of STZ-DM. Subsequently, the normal diet was continued or a low NaCl diet was initiated and 1 week later animals were prepared for clearance experiments under anesthesia including ureter catheterization to measure GFR for each kidney. In diabetic rats, the right innervated as well as the left denervated kidney showed higher values for GFR and kidney weight in animals on a low versus a normal NaCl diet indicating that the salt paradox occurs independent of renal innervation. In addition, evidence is provided that the renal nerves of non-diabetic rats do not contribute to renal Na(+) retention during dietary NaCl restriction but modulate renal hemodynamics and kidney weight under these conditions.     

On the control of renin release.

The role of carotid, aortic and cardiopulmonary receptors and of prostaglandins in the control of renin release was reviewed. It is suggested that the receptors in the low- and high-pressure circuits of the cardiovascular system control renin release through the renal sympathetic nerves and adrenal medulla. It is suggested that prostaglandins play a role in the control of renin release under certain pathophysiological conditions.     

经皮射频导管消融肾脏去交感神经支配术治疗顽固性高血压

目的总结经皮射频导管消融肾脏去交感神经支配治疗顽固性高血压的效果和前景。方法通过文献检索,总结肾脏交感神经与高血压的关系,经皮射频导管消融肾脏去交感神经支配术在治疗顽固性高血压中的应用,以及此项技术的前景和不足。结果高血压作为一个严重的公共卫生问题,是目前临床治疗的重点。肾脏交感神经在血压调控的各方面都扮演着重要的角色,经皮射频导管消融肾脏去交感神经支配术在治疗顽固性高血压方面展示了极大的优越性。结论经皮射频导管消融肾脏去交感神经支配术在治疗顽固性高血压方面有着潜在的临床应用价值。     

The sympathetic nervous system in clinical and experimental hypertension

In summary, many lines of evidence indicate that the sympathetic nervous system, via the renal nerves, plays an important role in the pathogenesis of renovascular hypertension in humans and laboratory animals. Patients with established renovascular hypertension have increased sympathetic nervous system activity, as evidenced by increased plasma and urinary norepinephrine levels, elevated excretion of catecholamine metabolites, and an exaggerated depressor response to centrally acting sympatholytic agents. The observation that converting enzyme inhibitors can cause both blood pressure and urinary norepinephrine excretion to return to normal in patients with renovascular hypertension is consistent with the interpretation that activation of the sympathetic nervous system in these subjects is, at least in part, angiotensin-induced. The sympathetic nervous system, via the efferent renal nerves, plays a role in the pathogenesis of hypertension in a number of experimental models. In the spontaneously hypertensive rat of the Okamoto strain (SHR) and in the DOCA/NaCl hypertensive model, increased renal efferent nerve activity contributes to the development of hypertension by causing increased renal sodium retention. In both of these experimental models, renal denervation delays the development and blunts the severity of hypertension. This delay is associated with increased urinary sodium excretion, suggesting a renal efferent mechanism. In contrast to the predominantly efferent renal nerve mechanisms observed in the DOCA-NaCl and SHR models, studies of the effects of renal denervation in one-kidney, one-clip and two-kidney, one-clip Goldblatt hypertensive rats suggest that renal afferent nerves are important in these models of hypertension. Total renal denervation in rats with established 1K, 1C and 2K, 1C hypertension attenuates the severity of the hypertension without altering sodium intake or excretion, renin activity, water intake, or renal function. Thus, efferent renal nerve activity does not appear to be involved in the development of maintenance of 1K, 1C or 2K, 1C hypertension. In contrast with the findings in SHR and DOCA-NaCl rats, these studies provide indirect evidence that the renal afferent nerves play a role in the pathogenesis of this form of experimental hypertension. The major effect of renal denervation in these models appears to be an interruption of renal afferent nerve activity, which by a direct feedback mechanism attenuates systemic sympathetic tone, thereby lowering blood pressure.(ABSTRACT TRUNCATED AT 400 WORDS)     

Renovascular hypertension from renal artery compression by congenital bands.

Renal artery compression by fibromuscular bands containing sympathetic nerves and ganglia was encountered in 3 of 75 patients with renovascular hypertension. The hypertension was successfully managed by resection of the bands. The absence of mortality and morbidity dictates that the "stenotic" area of the renal artery be explored, especially in children and adults with minimal angiographic evidence of visceral atherosclerosis, before proceeding with a bypass graft to the renal artery.     

Renal innervation and denervation: lessons from renal transplantation reconsidered

Renal transplantation assures complete denervation of the kidney. Human renal transplantation provided an opportunity to examine the consequences of renal denervation on renal functional capacity in human subjects. These initial studies led to an anatomical and physiological assessment of the time course of renal neural degeneration and reinnervation following renal transplantation or surgical division of the renal nerves. Together with a growing body of information concerning the extensive intrinsic innervation of the kidney's structural components, there has developed a comprehensive understanding of the overall neural control of kidney function.     

Radiation induced renal arterial stenosis detected by color duplex ultrasonography: case report

The renal arterial injury , a rare complicatiofrom radiation therapy has been in literatures[1-3]Depending upon the region being irradiated,arteriadamage may occur inrenal artery and other sites sucas the carotid artery[4 ,5],coronary artery[6]abdominal aorta , mesentery artery[7 ,8]. We had a patienwith renal artery stenosis caused by radiation therapy , which was initially detected by color duplex ultrasonography .1Case ReportA59 years old male was under the care of aninternist for hyperten…     

Effect of dopamine on renal haemodynamics in the denervated dog kidney

Summary The aim of the present study was to explore the potential modulating role of the renal sympathetic nerves in the dopamine-induced vasodilatation in the dog kidney, using the 133-Xenon washout technique.Immediately before and 48 h after combined surgical and local chemical destruction of the sympathetic nerves innervating the left kidney, renal and intrarenal blood flow was monitored in both kidneys. Catecholamine content was determined in control kidneys from untreated dogs, and in the denervated and contralateral, nondenervated kidney 48 h after unilateral sympathectomy.By 48 h after destruction of the sympathetic nerves innervating the left kidney, total renal and particularly cortical flow rates were significantly increased when compared to the right, innervated kidney. Destruction of the sympathetic nerves also resulted in a disappearance of noradrenaline and adrenaline from the kidney and a significant reduction in the content of dopamine in the denervated but an increased level in the innervated kidney.The dopamine-induced increase in renal blood flow was similar in the denervated and in the innervated kidney, suggesting that the sympathetic nerves do not significantly alter the vascular effects of dopamine. The persistence of the dopamine-induced vasodilatation in the sympathectomized kidney supports the concept that dopamine acts directly on postsynaptic, specific dopamine receptors.     

Unilateral renal angiodysplasia in a girl with hypertension

We report a case of very unusual renal vascular anomaly: angiodysplasia. The patient suffered from acute pyelonephritis immediately after birth. Renal ultrasonography, performed at age 1 day, revealed an enlarged left kidney with heterogeneously increased echogenicity, which involuted rapidly in 3 months. At age 10 years, she presented with severe hypertension during a course of acute pyelonephritis. Peripheral plasma renin activity was high. Computed tomographic angiogram revealed a very small but functioning left kidney. A single, narrow, left renal artery did not have focal stenosis. Pathology examination revealed dysplastic arterioles at the subcapsular area. After left nephrectomy, the blood pressure and the plasma renin activity were normalized. In conclusion, this is an unusual case of renal angiodysplasia, which induced renin-dependent hypertension.     

白细胞介素6mRNA在移植肾中的表达及意义

目的 探讨肾移植急性排斥反应时白细胞介素6(IL-6)产生的主要来源,并为初步阐明肾移植急性排斥反应的分子学发病机制提供实验依据。方法 采用3＇IL-6寡核苷酸探针,运用原位杂交技术观察IL-6mRNA在移植肾中的表达。结果 (1)在急性排斥反应时,移植肾各部位表达IL-6mRNA明显增多,较环孢素A(CsA)中毒、稳定期移植肾及正常人均有显著升高。(2)在急性排斥反应时,肾小管上皮细胞表达IL-6mRNA强度较肾小球细胞、血管内皮细胞及间质细胞均有明显升高。(3)CsA中毒患者肾脏IL-6mRNA表达较稳定期移植肾及正常对照无明显增多。结论 肾移植急性排斥反应时,移植肾细胞可直接产生IL-6,移植肾中IL-6异常激活与表达同肾移植急性排斥反应的发生机制有密切的关系;肾小管表达IL-6的异常增多和活化揭示了肾小管上皮细胞在肾移植急性排斥反应的发病机理中具有重要意义。     

Severe hyperreninemic hypertension associated with spontaneous renal cholesterol crystal embolization

A 70-year-old man was admitted because of severe hypertension and renal insufficiency. Marked elevation in plasma renin activity (PRA; 34.2ng/ml per h) was noted. Five days later, the patient developed hemorrhagic duodenal ulcers and panperitonitis, went into shock, and died. An autopsy revealed severe atherosclerosis with marked ulceration in the abdominal aorta. Renal histology showed multiple cholesterol crystal embolization (CCE) associated with infarction. Cholesterol crystals were also detected in the vessels of the gastrointestinal system, including the liver, stomach, colon, and pancreas. Although not common, spontaneous CCE should be considered in elderly patients who present with abrupt onset of severe hypertension associated with renal insufficiency. The most important finding in this patient was severe hyperreninemia. Although potentiation of the renin-angiotensin-aldosterone system is the suggested mechanism for the hypertension in renal CCE, we could not find any reported case of renal CCE with hyperreninemia. It is reasonable to consider that severe hyperreninemia might be overlooked in renal CCE. PRA should be measured in patients with renal CCE, because it may give important information for selecting antihypertensive agents and improving the prognosis. To clarify this possibility, an accumulation of similar cases is necessary.     

Effect of hypercalcemia on renal sympathetic nervous system activity.

Since calcium plays a modulatory role in the activity of the sympathetic nervous system (SNS), in these studies, we have tested the hypothesis that hypercalcemia may alter renal SNS activity, and, consequently, renal function. Acute hypercalcemia was induced in Sprague-Dawley rats by infusion of calcium 30 mg/kg/2 h in 0.45% saline. A control group of rats received only 0.45% saline. Two more groups of rats received either calcium or 0.45% saline 7-10 days after total renal denervation. Calcium infusion increased serum calcium by 1.8 +/- 0.23 mg/dl in rats with intact renal nerves and by 2.7 +/- 0.48 mg/dl in renal denervated rats. Mean arterial pressure and inulin clearance did not change during calcium or 0.45% saline in rats with intact renal nerves. Renal sympathetic nerve activity (RSNA) decreased by 44% in rats infused with calcium, but it did not change in control animals. Calcium caused a significantly greater rise in urine volume, sodium excretion and fractional excretion of sodium than the infusion of 0.45% saline. Rats with renal denervation manifested greater baseline urine volume, sodium excretion and fractional excretion of sodium than rats with intact renal nerves. Infusion of calcium, however, caused no further rise in urine sodium excretion in these animals. alpha-Methyltyrosine, an inhibitor of norepinephrine (NE) synthesis, also increased natriuresis in rats. Calcium reduced by 27% the NE content in the kidney but not in the heart. Methyltyrosine, on the other hand, reduced NE content in both the heart and the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)