thromboxane-b2 and Cardiomegaly

Actions of the lipid mediator thromboxane (Tx) A2 acting through the TP receptor contribute to the pathogenesis of cardiovascular disease. To further explore the role of TxA2 in hypertension, we examined the consequences of deficiency of the TP receptor on the course of hypertension associated with endothelial dysfunction and salt sensitivity. To this end, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was administered to TP-deficient (Tp-/-) and wild-type (Tp+/+) control mice in drinking water for 21 wk along with a high-salt (HS; 6% NaCl) diet. Administration of L-NAME increased urinary excretion of TxB2 to a similar extent in both Tp+/+ and Tp-/- animals. L-NAME also caused significant and sustained elevations in blood pressure that reached a maximum between weeks 3 and 6. However, the severity of hypertension was attenuated in the Tp-/- mice throughout the study period (P<0.001). At the end of the study, the wild-type mice developed significant cardiac hypertrophy (23.6+/-2% increase in heart-to-body weight ratio). The severity of cardiac hypertrophy was attenuated in the TP-deficient group (11.1+/-2.6%; P<0.05). In contrast, kidney hypertrophy was exaggerated in the Tp-/- mice compared with controls (37.1+/-5.4 vs. 12.3+/-2.3%; P<0.01). Moreover, the severity of glomerulosclerosis, tubule vacuolization, and interstitial chronic inflammation was also enhanced in the Tp-/- group (P<0.01). Thus, in L-NAME hypertension, TP receptors contribute to elevated blood pressure and cardiac hypertrophy. In this model, TP receptors also provided unexpected protection against kidney injury.

Topics: Albuminuria; Animals; Blood Pressure; Cardiomegaly; Disease Models, Animal; Drinking; Eating; Enzyme Inhibitors; Hypertension, Renal; Isoprostanes; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; NG-Nitroarginine Methyl Ester; Nitric Oxide; Receptors, Thromboxane A2, Prostaglandin H2; Renin-Angiotensin System; Sodium, Dietary; Thromboxane B2

The present study was designed to test the hypothesis that inflammation is involved in the end-organ damage (EOD) induced by sinoaortic denervation (SAD) in rats.. SAD was performed in male Sprague-Dawley rats at the age of 10 weeks. Under anaesthesia, aortic nerves were cut and the sinus region of the carotid artery was stripped and painted with 10% phenol. Pathological evaluation of EOD and the determination of plasma or tissue levels of the factors related to inflammation, including thromboxane B2 (TXB2) interleukin-1 (IL-1), tumour necrosis factor alpha (TNF-alpha) and reactive oxygen species (ROS) were performed at 16 weeks after SAD. Pathological evaluation of EOD included heart weight ratio, myocardial and blood vessel hydroxyproline and collagen volume fraction, glomerular injury score and number of infiltrating inflammatory cells. Indomethacin (20 mg/kg per day, orally) or vitamin E (100 mg/kg per day, orally) was administered for 12 weeks, beginning from 4 weeks after SAD, to observe their effects on SAD-induced EOD.. There were significant fibrosis and inflammatory infiltration in the myocardium and blood vessels, represented by higher hydroxyproline and collagen volume fraction, and a large amount of inflammatory cells in the tissues of SAD rats. Heart weight and kidney glomerular injury score were significantly higher in SAD than in sham-operated rats. Plasma TXB2, TNF-alpha, IL-1 and tissue ROS increased significantly after SAD. Indomethacin and vitamin E significantly decreased the contents of some factors related to inflammation in SAD rats. Both drugs also alleviated myocardial and vessel fibrosis, inflammatory infiltration and kidney damage.. Inflammation is involved in the organ damage induced by SAD in rats.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Aorta; Blood Vessels; Cardiomegaly; Collagen; Denervation; Fibrosis; Hydroxyproline; Indomethacin; Inflammation Mediators; Interleukin-1; Kidney; Kidney Glomerulus; Male; Myocardium; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Sinus of Valsalva; Thromboxane B2; Tumor Necrosis Factor-alpha; Vitamin E