atrial-natriuretic-factor and ozagrel

We have previously reported an increase in plasma levels of atrial natriuretic factor (ANF) in an ovine model of endotoxemia. The purpose of this study was to determine if this IR-ANF release was mediated by the increase of right atrial pressure (RAP) and right heart volumes concomitantly observed following endotoxin (LPS) administration. We studied right ventricular function, renal blood flow (RBF), urinary output (UO), urinary clearance of free water (CH20), urinary osmolality (UOSM), sodium excretion (UENA), and the plasma IR-ANF concentration (radioimmunoassay), following the administration of an E. coli LPS bolus (1 microgram/kg) with (group O, n = 8) and without (group E, n = 10) pretreatment with OKY-046, a selective thromboxane synthetase inhibitor. LPS induced early increases in RAP, right ventricular end-systolic (RVESV) and end-diastolic (RVEDV) volumes, heart rate (HR), and IR-ANF, and delayed increases in RBF, UO, and CH20. OKY-046 prevented the elevation of RAP, RVEDV, and RVESV; however, both groups showed virtually identical increases in IR-ANF (E: 20.03 +/- 3.8 to 192.33 +/- 35.47 pg/ml, O: 17.9 +/- 4.1 to 159.5 +/- 23 pg/ml) as well as an increase of HR, RBF, UO, and CH20. The increase in IR-ANF release noted following the administration of LPS in an ovine model does not appear to be related to the early elevations in right heart volumes or atrial distension.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Disease Models, Animal; Diuresis; Endotoxins; Heart Rate; Lipopolysaccharides; Methacrylates; Natriuresis; Osmolar Concentration; Renal Circulation; Sheep; Thromboxane-A Synthase; Toxemia; Urine; Vascular Resistance; Ventricular Function, Right

We used a chronic instrumented ovine model to investigate right heart function following an endotoxin bolus. Primary aim of the experiments was to elucidate the influence of the right heart on the cardiopulmonary system. Furthermore, we tried a thromboxane synthetase inhibitor as a therapeutical approach. At least we investigated the IR-ANF release, as the endocrinal function of the right heart, in this model. Following the endotoxin administration we observed a massive increase of the pulmonary arterial pressure. As a result of the increased right ventricular afterload right ventricular ejection fraction decreased and end-systolic volume increased. Impaired right heart function could not be compensated sufficiently using Frank Starling mechanism. Consequently, decreased left ventricular preload, stroke volume and cardiac output followed. Pretreatment with OKY-046, a selective thromboxane synthase inhibitor, attenuated the increase in pulmonary arterial pressure and prevented the early right heart failure including the drop of cardiac output. Furthermore, OKY-046 changed the thromboxane-prostacyclin relationship. Therefore we consider the cardiopulmonary reactions following pretreatment with OKY-046 as a result of the attenuated right ventricular afterload as well as of the increased prostacyclin concentration. Endotoxin induced hypoxaemia could not be prevented by pretreatment with OKY-046 and might be caused by interstitial edema following endothelial leakage. IR-ANF release in our model, accompanied by polyuria and natriuresis, seemed to be independent of right heart dysfunction and increase of right atrial pressure. We suggest endotoxin or a endotoxin induced mediator as a trigger of IR-ANF release.

Topics: Animals; Atrial Natriuretic Factor; Endotoxins; Escherichia coli; Heart Function Tests; Hemodynamics; Kidney; Methacrylates; Pulmonary Circulation; Pulmonary Wedge Pressure; Sheep; Thromboxane-A Synthase; Toxemia; Ventricular Function, Right

Topics: Atrial Natriuretic Factor; Dioxolanes; Dipeptides; Female; Humans; Methacrylates; Pre-Eclampsia; Pregnancy; Thromboxane-A Synthase

The present studies were designed to analyze the potential contribution of angiotensin II and thromboxane A2 to the remarkable decrease in glomerular filtration rate (GFR) and renal plasma flow observed after unilateral release of 24-hour bilateral ureteral obstruction. Pretreatment of the animals with inhibitors of either thromboxane or angiotensin synthesis for 48 hours prior to and during obstruction eliminated the contribution of these vasoconstrictors. Inhibition of these vasoconstrictors during the period of obstruction results in a greater increase in renal plasma flow and GFR than when inhibition was accomplished after release of the obstruction. These data suggest a greater role for these vasoconstrictors in the decrease in GFR that occurs with obstruction. Simultaneous inhibition of thromboxane and angiotensin production normalized GFR of the postobstructed kidney. Administration of atrial peptide after release of obstruction in the different groups of rats resulted in further increases in GFR, urine flow and absolute sodium excretion. It is suggested that atrial peptide participates in the renal hemodynamic changes that occur in the postobstructed kidney.

Topics: Acrylates; Animals; Atrial Natriuretic Factor; Enalapril; Female; Glomerular Filtration Rate; Kidney; Methacrylates; Rats; Rats, Inbred Strains; Reference Values; Thromboxane-A Synthase; Ureteral Obstruction; Vasoconstrictor Agents