Kynurenic acid selectively reduces heart rate in spontaneously hypertensive rats

We found previously that intravenous kynurenic acid (KYNA), a native broad spectrum glutamate antagonist, increases renal blood flow and induces natriuresis in anesthetized spontaneously hypertensive rats (SHR). Since such changes may affect systemic circulation and can potentially find therapeutic...

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Published in:Naunyn-Schmiedeberg's archives of pharmacology 2020-04, Vol.393 (4), p.673-679
Main Authors: Bądzyńska, Bożena, Zakrocka, Izabela, Turski, Waldemar A., Olszyński, Krzysztof H., Sadowski, Janusz, Kompanowska-Jezierska, Elżbieta
Format: Article
Language:English
Subjects:
Animals
Arterial Pressure - drug effects
Biomedical and Life Sciences
Biomedicine
Blood flow
Blood pressure
Cardiovascular diseases
Coronary artery disease
Dietary supplements
Diuresis
Drinking water
Excretion
Heart diseases
Heart rate
Heart Rate - drug effects
Hemodynamics
Hypertension
Hypertension - physiopathology
Intravenous administration
Kidney - drug effects
Kidney - pathology
Kidney - physiology
Kidneys
Kynurenic acid
Kynurenic Acid - pharmacology
Male
Myocardium - pathology
Neurosciences
Oral administration
Original Article
Pharmacology/Toxicology
Rats, Inbred SHR
Renal function
Risk factors
Sodium - physiology
Tachycardia
Telemetry
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Summary:We found previously that intravenous kynurenic acid (KYNA), a native broad spectrum glutamate antagonist, increases renal blood flow and induces natriuresis in anesthetized spontaneously hypertensive rats (SHR). Since such changes may affect systemic circulation and can potentially find therapeutic application, in this study we examined long term influence of orally administered KYNA on systemic and renal hemodynamics and renal excretion in conscious SHR. KYNA was administered in drinking water at a dose of 25 mg/kg/day for 3 weeks. Heart rate (HR), systolic (SBP), and mean arterial pressure (MAP) were measured through telemetry. The records were taken at the beginning of the study (control, day 0), and then on day 7, 14, and 21 of treatment. Diuresis (V), total solute excretion (U osm V), and sodium excretion (U Na V) were determined on days 0, 7, and 14. KYNA consistently decreased HR, from 319 ± 8 to 291 ± 5, 299 ± 9 and 284 ± 6 beats/min on day 7, 14, and 21, respectively, (− 9, − 6, and − 11%; p  
ISSN:0028-1298
1432-1912
DOI:10.1007/s00210-019-01771-7