title: Effects of systemic administration of kynurenic acid and glycine on renal haemodynamics and excretion in normotensive and spontaneously hypertensive rats.
abstract: Both NMDA receptor and kynurenic acid (KYNA), a glycine-site NMDA receptor antagonist, are present in the kidney yet their functional role remains unclear. Our aim was to examine effects of intravenous KYNA and glycine on arterial blood pressure (MAP) and renal haemodynamics and excretion in anaesthetized normotensive Sprague-Dawley (S-D) and in spontaneously hypertensive (SHR) rats. Renal blood flow (RBF, renal artery probe) and renal cortical (CBF) and outer- and inner medullary perfusion (laser-Doppler) were measured, along with diuresis (V) and sodium excretion (UNaV). KYNA given alone (150mgkg(-1) iv) or during infusion of glycine at 1gkg(-1)h(-1) iv (G+K) increased or decreased RBF, respectively, in both S-D and SHR. Neither treatment altered MAP. In both strains glycine alone increased RBF and CBF 50-60% and was clearly diuretic and natriuretic, less so in SHR. KYNA increased UNaV by 4.1±1.7μmolmin(-1)and V by 11.1±4.3μlmin(-1) in S-D (P<0.05 for both); the respective increases in SHR were by 1.7±0.6μmolmin(-1) and 4.7±1.7μlmin(-1) (P<0.02 for both). G+K treatment increased UNaV by 5.2±1.4μmolmin(-1) (P<0.01) and V by 29.6±4.6μmolmin(-1) (P<0.001) in S-D, and by 2.7±0.7μmolmin(-1) (P<0.05) and 19.3±3.5μlmin(-1) (P<0.0006) in SHR. In conclusion, KYNA increased renal excretion, apparently by inhibiting tubular reabsorption, whereas glycine substantially increased renal haemodynamics by an ill-defined mechanism, with a secondary increase in the excretion. Combined G+K treatment could be utilised to combat body fluid retention and possibly alleviate hypertension, without endangering renal perfusion and function.
authors.affiliation: Department of Renal and Body Fluid Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland.
authors.forename: Bożena
authors.initials: B
authors.lastname: Bądzyńska
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University, Ceramiczna 1, 20-150 Lublin, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Zakrocka
authors.affiliation: Department of Renal and Body Fluid Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Sadowski
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University, Ceramiczna 1, 20-150 Lublin, Poland.
authors.forename: Waldemar A
authors.initials: WA
authors.lastname: Turski
authors.affiliation: Department of Renal and Body Fluid Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, Poland. Electronic address: ellakomp@gmail.com.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Kompanowska-Jezierska
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D005998:Glycine / Q000008:administration & dosage*; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects*; D007736:Kynurenic Acid / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism
chemical_list: D012964:Sodium; D007736:Kynurenic Acid; D005998:Glycine
keywords: Glycine; Kynurenic acid; Renal excretion; Renal haemodynamics