thromboxane-a2 and Renal-Insufficiency

Patients surviving an acute coronary syndrome (ACS) remain at increased risk of ischemic events long term. This paper reviews current evidence and guidelines for oral antiplatelet therapy for secondary prevention following ACS, with respect to decreased risk of ischemic events versus bleeding risk according to individual patient characteristics and risk factors. Specifically, data are reviewed from clinical studies of clopidogrel, prasugrel, ticagrelor and vorapaxar, as well as the results of systematic reviews and meta-analyses looking at the benefits and risks of oral antiplatelet therapy, and the relative merits of shorter versus longer duration of dual antiplatelet therapy, in different patient groups.

Topics: Acute Coronary Syndrome; Adenosine Diphosphate; Administration, Oral; Aging; Blood Platelets; Cyclooxygenase 1; Diabetes Mellitus; Drug Administration Schedule; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Purinergic P2Y Receptor Antagonists; Receptor, PAR-1; Receptors, Purinergic P2Y12; Renal Insufficiency; Risk Factors; Secondary Prevention; Thrombin; Thromboxane A2; Time Factors; Vascular Diseases

This study was designed to investigate the role of eicosanoids, thromboxane A2 (TXA2) and prostacyclin (PGI2) as well as their relationship with endothelin-1 (ET-1) in the pathogenesis of renal parenchymal hypertension. Uremic rats were prepared by renal mass ablation and compared with sham-operated controls. The stable metabolites of TXA2 (TXB2) and PGI2 (6-keto-PGF1alpha) and immunoreactive ET-1 concentrations were measured by specific RIAs in biological fluids and in vascular and renal tissues. To investigate the functional role of TXA2 in the progression of hypertension and renal failure, a group of uremic rats were treated with ridogrel (25 mg/kg/day), a TXA2 synthase inhibitor and receptor antagonist. Renal preproET-1 expression was assessed by Northern blot analysis. Systolic blood pressure (SBP), serum creatinine and proteinuria were found to be higher in uremic rats as compared to sham-operated controls (P < 0.01). TXB2 and ET-1 concentrations were increased in blood vessels, the renal cortex and in urine (P < 0.05). 6-keto-PGF1alpha concentrations were also increased in blood vessels and the renal cortex but decreased in urine (P < 0.05). Ridogrel significantly lowered SBP and proteinuria (P < 0.05) and blunted the increase of serum creatinine. Treatment with ridogrel resulted in a marked fall in vascular, renal and urine TXA2 concentrations, while ET-1 and 6-keto-PGF1alpha concentrations remained unchanged. The preproET-1 expression was higher in uremic rats than in the controls and was unaffected by ridogrel. These results suggest that TXA2 is involved in the pathogenesis of hypertension and renal failure progression in rats with subtotal 5/6 nephrectomy and that this effect is independent of the ET-1 system.

Topics: Animals; Blood Pressure; Disease Models, Animal; Disease Progression; Eicosanoids; Endothelin-1; Epoprostenol; Male; Rats; Rats, Wistar; Renal Insufficiency; Thromboxane A2; Time Factors; Uremia

Haemodynamic changes in partial unilateral ureteric obstruction (PUUO) may be related to altered prostaglandin synthesis. In 12 dogs the left ureter was partially obstructed for 5 weeks. In six dogs the ureter was reimplanted into the bladder and to investigate the effect of this procedure on the contralateral side the other six animals underwent ipsilateral nephroureterectomy. Renal blood flow (RBF) was measured by the distribution of radiolabelled microspheres. Changes in urinary prostaglandin (PG) concentrations were validated by renin activity using angiotensin I. Reduced left RBF during obstruction was associated with increased thromboxane A2 synthesis (P < 0.01). Increased RBF to the non-obstructed side was associated with elevated PGE2 formation (P < 0.05). Elevated angiotensin I levels (P < 0.01) corresponded to maximal increases in PG synthesis. Reimplantation of the obstructed kidney did not exert a direct effect on contralateral RBF or PG concentration. Haemodynamic changes in PUUO in vivo are associated with alterations in renal PGs.

Topics: Angiotensin I; Animals; Dinoprostone; Dogs; Hemodynamics; Prostaglandins; Renal Insufficiency; Thromboxane A2; Ureteral Obstruction