{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:17:15Z","timestamp":1753892235037,"version":"3.41.2"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Hitherto, the rabbit has long been known to have a very poor tolerance to non\u2014volatile acid. In this study, we tested the hypothesis that acid resilience in the acidotic rabbit can be increased by enhancing the plasma availability of a naturally occurring volatile fatty acid, namely acetate. To ascertain the relative merits of the respiratory and renal systems in contributing to that resilience, we conducted our studies in non\u2014ventilated and mechanically ventilated acidotic animals. Using ethanol as a feeder of acetate, and to counteract the antidiuretic effects of surgical interventions, we induced acidosis in anaesthetised rabbits, by intravenously infusing an acidified ethanolic dextrose solution. We observed very potent respiratory regulation of arterial blood pH coupled with a notable renal response by way of a 25-fold increase in urinary ammonium excretion in the non\u2014ventilated group. In contrast, arterial blood pH plummeted much more rapidly in the mechanically\u2014ventilated animals, but the compensated renal response was enormous, in the form of an 85 -fold increase in urinary ammonium output. Despite this significant adaptive renal response, the non -mechanically ventilated group of rabbits showed the greater acid resilience. This was attributed to an acetate stimulated flux through a series of metabolic pathways, generating supplementary buffer in the form of bicarbonate and ammonia, complemented by a robust respiratory response.<\/jats:p>","DOI":"10.3389\/fphys.2022.860042","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T06:46:50Z","timestamp":1665557210000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Infusion of an acidified ethanolic\u2014dextrose solution enhances urinary ammonium excretion and increases acid resilience in non\u2014mechanically ventilated acidotic rabbits"],"prefix":"10.3389","volume":"13","author":[{"given":"Patrick A.","family":"Walsh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1172\/JCI104285","article-title":"The effect of buffer loading upon ammonium excretion in the dog","volume":"40","author":"Bank","year":"1961","journal-title":"J. Clin. Invest."},{"key":"B2","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1152\/physrev.1990.70.2.567","article-title":"Energy contributions of volatile fatty acids from the gastrointestinal tract in various species","volume":"70","author":"Bergman","year":"1990","journal-title":"Physiol. Rev."},{"volume-title":"The energy metabolism of ruminants","year":"1962","author":"Blaxter","key":"B3"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1152\/ajplegacy.1972.223.6.1354","article-title":"Comparative study of Pa CO2 in several homeothermic species","volume":"223","author":"Chapot","year":"1972","journal-title":"Am. J. Physiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"4705","DOI":"10.1074\/jbc.272.8.4705","article-title":"The rabbit kidney tubule simultaneously degrades and synthesizes glutamate. A 13C NMR study","volume":"272","author":"Chauvin","year":"1997","journal-title":"J. Biol. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1111\/j.1432-1033.1979.tb13279.x","article-title":"Role of the mitochondrial anion transporters in the regulation of ammoniagenesis in renal cortex mitochondria of the rabbit and rat","volume":"99","author":"Cheema-Dhadli","year":"1979","journal-title":"Eur. J. Biochem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"29444","DOI":"10.1074\/jbc.M111335200","article-title":"The anaplerotic substrate alanine stimulates acetate incorporation into glutamate and glutamine in rabbit kidney tubules. A (13)C NMR study","volume":"277","author":"Conjard","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/ki.1974.41","article-title":"A comparison of methods for measuring urinary ammonium","volume":"5","author":"Cunarro","year":"1974","journal-title":"Kidney Int."},{"key":"B9","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1042\/bj3420555","article-title":"Acetate stimulates flux through the tricarboxylic acid cycle in rabbit renal proximal tubules synthesizing glutamine from alanine: A 13C NMR study","volume":"342","author":"Dugelay","year":"1999","journal-title":"Biochem. J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"16S","DOI":"10.1111\/j.1530-0277.2000.tb00005.x","article-title":"Michaelis-Menten elimination kinetics of acetate during ethanol oxidation","volume":"24","author":"Fujimiya","year":"2000","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"B11","first-page":"311","article-title":"Parallel first-order and Michaelis-Menten elimination kinetics of ethanol. Respective role of alcohol dehydrogenase (ADH), non-ADH and first-order pathways","volume":"249","author":"Fujimiya","year":"1989","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B13","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1152\/ajplegacy.1947.150.1.70","article-title":"Measurement of the respiratory volumes of laboratory animals","volume":"150","author":"Guyton","year":"1947","journal-title":"Am. J. Physiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/0020-711x(80)90056-7","article-title":"Regulation of renal ammoniagenesis in the rabbit","volume":"12","author":"Halperin","year":"1980","journal-title":"Int. J. Biochem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1681\/ASN.2010050468","article-title":"Aldosterone requires vasopressin V1a receptors on intercalated cells to mediate acid-base homeostasis","volume":"22","author":"Izumi","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1152\/ajplegacy.1955.182.1.131","article-title":"Regulation of ammonia excretion in the rat","volume":"182","author":"Leonard","year":"1955","journal-title":"Am. J. Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1002\/bjs.1800760512","article-title":"Measurement of body water compartments after ligation of the common bile duct in the rabbit","volume":"76","author":"Mart\u00ednez-R\u00f3denas","year":"1989","journal-title":"Br. J. Surg."},{"key":"B18","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1042\/bj2970069","article-title":"Glutamine synthesis from glucose and ammonium chloride by Guinea-pig kidney tubules","volume":"297","author":"Michoudet","year":"1994","journal-title":"Biochem. J."},{"key":"B19","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/B978-0-12-409527-4.00010-9","article-title":"Biology and diseases of rabbits","volume-title":"Laboratory animal medicine","author":"Nowland","year":"2015"},{"key":"B20","doi-asserted-by":"publisher","first-page":"135","DOI":"10.2215\/CJN.05760513","article-title":"Collecting duct principal cell transport processes and their regulation","volume":"10","author":"Pearce","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1152\/ajplegacy.1958.192.2.392","article-title":"Ammonia excretion of the Guinea pig and rabbit","volume":"192","author":"Richterich","year":"1958","journal-title":"Am. J. Physiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1152\/ajplegacy.1958.195.2.316","article-title":"Distribution of glutamine metabolizing enzymes and production of urinary ammonia in the mammalian kidney","volume":"195","author":"Richterich","year":"1958","journal-title":"Am. J. Physiol."},{"key":"B25","first-page":"205","article-title":"Respiratory rates and arterial blood-gas tensions in healthy rabbits given buprenorphine, butorphanol, midazolam, or their combinations","volume":"50","author":"Schroeder","year":"2011","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.2215\/CJN.05920613","article-title":"Distal convoluted tubule","volume":"9","author":"Subramanya","year":"2014","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"F259","DOI":"10.1152\/ajprenal.1998.274.2.F259","article-title":"Carbonic anhydrase II and IV mRNA in rabbit nephron segments: Stimulation during metabolic acidosis","volume":"274","author":"Tsuruoka","year":"1998","journal-title":"Am. J. Physiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1111\/jpn.13143","article-title":"An appraisal of the in vivo role of phosphate as a modulator of urinary ammonium and titratable acid excretion in the acidotic rabbit","volume":"103","author":"Walsh","year":"","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"B31","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/laban.953","article-title":"Collection of untainted urinary specimens from the bladder of an anesthetized rabbit.","volume":"45","author":"Walsh","year":"2016","journal-title":"Lab. Anim."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3988","DOI":"10.1038\/s41598-020-61069-0","article-title":"The kinetics of inorganic phosphate excretion in the acidotic rabbit during intravenous phosphate loading: A pseudo-ruminant model","volume":"10","author":"Walsh","year":"2020","journal-title":"Sci. Rep."},{"key":"B33","article-title":"The physiological conundrum of inorganic phosphate stimulation of urinary ammonium excfetion in the acidotic rabbit","volume-title":"Proceedings of the physiological society","author":"Walsh","year":""},{"key":"B34","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.2215\/CJN.10311013","article-title":"Urea and ammonia metabolism and the control of renal nitrogen excretion","volume":"10","author":"Weiner","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1152\/physrev.00011.2016","article-title":"Ammonia transporters and their role in acid-base balance","volume":"97","author":"Weiner","year":"2017","journal-title":"Physiol. Rev."},{"key":"B36","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1172\/JCI108501","article-title":"Stimulation of ammonia production and excretion in the rabbit by inorganic phosphate. Study of control mechanisms","volume":"58","author":"Yu","year":"1976","journal-title":"J. Clin. Invest."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.860042\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T06:46:58Z","timestamp":1665557218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.860042\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,12]]},"references-count":31,"alternative-id":["10.3389\/fphys.2022.860042"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.860042","relation":{},"ISSN":["1664-042X"],"issn-type":[{"type":"electronic","value":"1664-042X"}],"subject":[],"published":{"date-parts":[[2022,10,12]]},"article-number":"860042"}}