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 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_osmV), and sodium excretion (U_NaV) 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 < 0.01-0.0001); HR was stable in the solvent group. SBP, MAP, V, and U_NaV were not affected by KYNA, whereas U_osmV increased modestly. Chronic oral administration of KYNA to conscious SHR decreased HR without affecting MAP. Since tachycardia is an independent risk factor for cardiovascular disorders, and most drugs used to decrease HR have strong inotropic negative or hypotensive effect, such selective action seems of therapeutic potential. Moreover, food supplementation with KYNA can be considered in the prevention of heart diseases.