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Hypertension (Dallas, Tex. : 1979) Apr 1995We review evidence supporting the conclusion that renal dysfunction underlies the development of all forms of hypertension in humans and experimental animals. Indexes of... (Review)
Review
We review evidence supporting the conclusion that renal dysfunction underlies the development of all forms of hypertension in humans and experimental animals. Indexes of global renal function are generally normal in the early stages of most genetic forms of hypertension, but renal function is clearly impaired in long-established hypertension. Studies in our laboratory over the past decade summarized below have established that the renal medulla plays an important role in sodium and water homeostasis and in the long-term control of arterial pressure. Development of implanted optical fibers for measurement of cortical and medullary blood flows with laser-Doppler flowmetry and techniques for delivery of vasoactive compounds into the medullary interstitial space enabled us to examine determinants of medullary flow (nitric oxide, atrial natriuretic peptides, kinins, eicosanoids, vasopressin, renal sympathetic nerves, etc). We have shown in spontaneously hypertensive rats that the initial changes of renal function begin as a reduction of medullary blood flow in the absence of changes of cortical flow. Long-term medullary interstitial infusion of captopril, which preferentially increased medullary blood flow, resulted in a lowering of arterial pressure. In normal Sprague-Dawley rats, selective reduction of medullary flow with medullary interstitial or intravenous infusion of small amounts of NG-nitro-L-arginine methyl ester resulted in hypertension. These and other studies we review show that although blood flow to the inner renal medulla comprises less than 1% of the total renal blood flow, changes in flow to this region can have a major effect on sodium and water homeostasis and on the long-term control of arterial blood pressure.
Topics: Animals; Atrial Natriuretic Factor; Calcium Channel Blockers; Humans; Hypertension; Kidney Medulla; Laser-Doppler Flowmetry; Nitric Oxide; Peptide Fragments; Renal Circulation
PubMed: 7721413
DOI: 10.1161/01.hyp.25.4.663 -
Nephrologie & Therapeutique Apr 2016The ability to produce hyperosmotic urine allows mammals, including humans, to excrete their soluble mineral and organic waste products in the urine with a limited...
The ability to produce hyperosmotic urine allows mammals, including humans, to excrete their soluble mineral and organic waste products in the urine with a limited amount of water. The urinary concentrating capacity depends primarily on a special "loop-shaped" architecture of the nephrons and vessels, observed only in mammals. It also depends on the influence of antidiuretic hormone on the permeability to water of the collecting ducts on their entire length, and on the permeability to urea limited to the terminal portion of these ducts in the inner medulla. The ability to concentrate urine also requires (1) an "engine" able to produce an active (energy demanding) transport that generates a transepithelial concentration difference leading to increase the solute concentration in the surrounding interstitium; and (2) the expression of several membrane transporters or channels localized very specifically to limited portions of some nephron segments, collecting ducts and arterial vasa recta. These transporters and channels greatly accelerate the transport of water and some solutes across the cell membranes. Even if some nephron segments and parts of the collecting system are present in both the renal cortex and medulla (namely, the proximal tubule, the thick ascending limb and the collecting duct), their functions in the two renal zones may not be strictly similar, owing to their different peritubular environment, to the composition of the fluid running in their lumen, and to some differences in their epithelium. This paper describes some characteristics and specific functions of these structures in the renal medulla, as opposed to their corresponding structures in the cortex. These specific functions operating in the medulla may lead to various adverse consequences in some pathological situations.
Topics: Animals; Humans; Kidney Concentrating Ability; Kidney Medulla; Kidney Tubules; Nephrons; Urea; Urine
PubMed: 26976055
DOI: 10.1016/j.nephro.2016.02.010 -
Pathology, Research and Practice Apr 2015The renal medulla comprises an intricate system of tubules, blood vessels and interstitium that is not well understood by most general pathologists. We conducted an... (Review)
Review
The renal medulla comprises an intricate system of tubules, blood vessels and interstitium that is not well understood by most general pathologists. We conducted an extensive review of the literature on the renal medulla, in both normal and pathologic conditions. We set out in detail the points of key interest to pathologists: normal and pathological development, physiology, microscopic anatomy, histology and immunohistochemistry; and the specific and most common other types of disease associated with this part of the kidney: developmental abnormalities, (multicystic dysplastic kidney, autosomal dominant and recessive polycystic kidney diseases, medullary cystic kidney disease), inflammatory conditions (xanthogranulomatous pyelonephritis, malakoplakia), hyperplasia and dysplasia, and neoplastic processes (oncocytoma, atypical oncocytic tumors, chromophobe cell carcinoma, collecting duct carcinoma, urothelial carcinoma, other carcinomas, renal medullary fibroma and metastatic tumors). This condensed overview of the origin, function and pathology of the renal medulla, both in terms of development, inflammation and neoplastic processes, should help focus the interest of clinical pathologists on this widely overlooked part of the kidney.
Topics: Carcinoma; Humans; Immunohistochemistry; Kidney Diseases; Kidney Medulla; Kidney Neoplasms
PubMed: 25595996
DOI: 10.1016/j.prp.2014.12.009 -
Pediatric Nephrology (Berlin, Germany) Sep 2011The renal medulla, the inner compartment of the metanephric kidney, plays vital roles in the regulation of body water, electrolyte homeostasis, and systemic blood... (Review)
Review
The renal medulla, the inner compartment of the metanephric kidney, plays vital roles in the regulation of body water, electrolyte homeostasis, and systemic blood pressure. It is composed of the loops-of-Henle, the medullary collecting ducts, the vasa recta, and the medullary interstitium. Its epithelial and endothelial components display ordered spatial organization. This organization serves as the structural basis for its function in urine concentration. The urine concentration ability of a renal medulla is also related to its length among species. In this review, the current understanding of the molecular and cellular mechanisms underlying renal medulla formation (elongation) is summarized, with a focus on the role of Wnt signaling in this developmental process. Renal medulla blunting and effacement is a common symptom of many renal and urological destructions. The knowledge in renal medulla formation should assist efforts in repair and regeneration of a damaged renal medulla, so to improve renal physiology in diseased situations.
Topics: Animals; Gene Expression Regulation, Developmental; Humans; Kidney Medulla; Organogenesis; Signal Transduction; Wnt Proteins
PubMed: 21533626
DOI: 10.1007/s00467-011-1888-8 -
Circulation Research Nov 1985
Review
Topics: Animals; Blood Flow Velocity; Body Fluids; Hematocrit; Homeostasis; Humans; Kidney Medulla; Methods; Microcirculation; Microscopy; Microspheres; Prostaglandins; Radioisotopes; Serum Albumin; Television; Urination; Vasopressins
PubMed: 3902277
DOI: 10.1161/01.res.57.5.657 -
Comprehensive Physiology Jan 2012The renal medullary microcirculation is a distinctive arrangement of blood vessels that serve multiple functions in the renal medulla. This article begins with a... (Review)
Review
The renal medullary microcirculation is a distinctive arrangement of blood vessels that serve multiple functions in the renal medulla. This article begins with a description of the unique anatomy of this vascular bed and the role it plays in transport and countercurrent exchange in the medulla. A segment of the review is then devoted to the important role mathematical modeling has played in the understanding of this vascular bed's function. Succeeding sections focus upon the hematocrit in the vasa recta capillaries and methods utilized to assess blood flow in the renal medulla. An extensive portion of the article is then devoted to the regulation of the medullary circulation, from ion channel architecture to neurohormonal signaling. Finally, we discuss the importance of the renal medullary circulation in the regulation of fluid and electrolyte homeostasis and arterial blood pressure regulation.
Topics: Animals; Arterial Pressure; Biological Transport; Diagnostic Techniques, Urological; Hematocrit; Homeostasis; Humans; Ion Channels; Kidney Medulla; Microcirculation; Microscopy, Electron; Models, Cardiovascular; Natriuresis; Renal Circulation
PubMed: 23728972
DOI: 10.1002/cphy.c100036 -
Renal Physiology and Biochemistry 1988Cells of the renal medulla adapt osmotically to varying external electrolyte concentrations mainly by changing the intracellular content of small organic osmoeffectors... (Review)
Review
Cells of the renal medulla adapt osmotically to varying external electrolyte concentrations mainly by changing the intracellular content of small organic osmoeffectors (osmolytes) such as sorbitol, inositol and trimethylamines. This implies that despite extreme variations in extracellular tonicity the intracellular concentrations of monovalent electrolytes are stabilized at levels optimal for enzyme function and cell metabolism. In contrast to inorganic electrolytes these organic osmolytes are metabolically neutral and thus do not affect cell metabolism. In addition, some of these organic osmoeffectors, the trimethylamine compounds, are known to counteract the deleterious effects of high urea concentrations (prevailing in antidiuresis) on structure and function of cell proteins.
Topics: Animals; Kidney Medulla; Water-Electrolyte Balance
PubMed: 3074397
DOI: 10.1159/000173161 -
Acta Physiologica (Oxford, England) May 2013Adverse events during foetal development can predispose the individual for cardiovascular disease later in life, a correlation known as foetal programming of adult... (Review)
Review
Adverse events during foetal development can predispose the individual for cardiovascular disease later in life, a correlation known as foetal programming of adult hypertension. The 'programming' events have been associated with the kidneys due to the significant role in extracellular volume control and long-term blood pressure regulation. Previously, nephron endowment and functional consequences of a low nephron number have been extensively investigated without achieving a full explanation of the underlying pathophysiological mechanisms. In this review, we will focus on mechanisms of postnatal development in the renal medulla with regard to the programming effects. The renin-angiotensin system is critically involved in mammalian kidney development and impaired signalling gives rise to developmental renal lesions that have been associated with hypertension later in life. A consistent finding in both experimental animal models and in human case reports is atrophy of the renal medulla with developmental lesions to both medullary nephron segments and vascular development with concomitant functional disturbances reaching into adulthood. A review of current knowledge of the role of the renin-angiotensin system for renal medullary development will be given.
Topics: Age Factors; Angiogenic Proteins; Animals; Hemodynamics; Humans; Hypertension; Kidney Medulla; Microcirculation; Prognosis; Renal Circulation; Renin-Angiotensin System; Risk Factors; Signal Transduction; Urogenital Abnormalities
PubMed: 23432903
DOI: 10.1111/apha.12088 -
Blood Purification 1997
Review
Topics: Animals; Humans; Hypoxia; Kidney Medulla; Microcirculation
PubMed: 9435951
DOI: 10.1159/000170341 -
The American Journal of Physiology Jul 1997The original fascination with the medullary circulation of the kidney was driven by the unique structure of vasa recta capillary circulation, which Berliner and... (Review)
Review
The original fascination with the medullary circulation of the kidney was driven by the unique structure of vasa recta capillary circulation, which Berliner and colleagues (Berliner, R. W., N. G. Levinsky, D. G. Davidson, and M. Eden. Am. J. Med. 24: 730-744, 1958) demonstrated could provide the economy of countercurrent exchange to concentrate large volumes of blood filtrate and produce small volumes of concentrated urine. We now believe we have found another equally important function of the renal medullary circulation. The data show that it is indeed the forces defined by Starling 100 years ago that are responsible for the pressure-natriuresis mechanisms through the transmission of changes of renal perfusion pressure to the vasa recta circulation. Despite receiving only 5-10% of the total renal blood flow, increases of blood flow to this region of the kidney cause a washout of the medullary urea gradient and a rise of the renal interstitial fluid pressure. These forces reduce tubular reabsorption of sodium and water, leading to a natriuresis and diuresis. Many of Starling's intrinsic chemicals, which he named "hormones," importantly modulate this pressure-natriuresis response by altering both the sensitivity and range of arterial pressure around which these responses occur. The vasculature of the renal medulla is uniquely sensitive to many of these vasoactive agents. Finally, we have found that the renal medullary circulation can play an important role in determining the level of arterial pressure required to achieve long-term fluid and electrolyte homeostasis by establishing the slope and set point of the pressure-natriuresis relationship. Measurable decreases of blood flow to the renal medulla with imperceptible changes of total renal blood flow can lead to the development of hypertension. Many questions remain, and it is now evident that this is a very complex regulatory system. It appears, however, that the medullary blood flow is a potent determinant of both sodium and water excretion and signals changes in blood volume and arterial pressure to the tubules via the physical forces that Professor Starling so clearly defined 100 years ago.
Topics: Animals; Blood Pressure; Blood Volume; Capillaries; Homeostasis; Humans; Hypertension; Kidney Medulla; Models, Biological; Renal Circulation
PubMed: 9249526
DOI: 10.1152/ajpregu.1997.273.1.R1