thromboxane-b2 and Sclerosis

1. The effects of OKY-046, a specific thromboxane (TX) synthetase inhibitor, on blood pressure, urinary excretion of TX and its release from blood platelets and renal papilla, and pathological change of glomeruli were evaluated in Dahl salt-sensitive rats. 2. Average daily intakes of OKY-046-treated rats were 0.93 mg/kg (low dose), 9.8 mg/kg (moderate dose), and 88 mg/kg (high dose). 3. Systolic blood pressure tended to decrease by 6.3, 11.4, and 10.9% in three OKY-treated groups. 4. OKY-046 suppressed the release of TX from platelets in a dose-dependent fashion. Both TX in urine and released from renal papilla decreased in OKY-treated groups with moderate and high dose. OKY-046 resulted no change in urinary excretion or release from renal papilla of prostaglandin E2 or 6-keto-prostaglandin F1alpha. 5. Glomerular sclerosis score decreased significantly in both groups treated with moderate and high doses of OKY-046. 6. An inhibition of renal TX synthesis by TX synthetase inhibitor has a protective effect on the development of hypertensive renal damage with minor antihypertensive effect in Dahl salt-sensitive rats.

Topics: Animals; Antihypertensive Agents; Enzyme Inhibitors; Female; Hypertension; Kidney; Kidney Glomerulus; Methacrylates; Rats; Rats, Inbred Strains; Sclerosis; Sodium Chloride; Thromboxane B2; Thromboxane-A Synthase

Sclerosing peritonitis is a severe complication after CAPD treatment. The visceral peritoneum is thickened and interenteric adhesive parts are found. Myofibroblasts are proliferated and the collageneous tissue is hyperplastic. The mean clinical symptom is the mechanical obstruction of the small bowel. We observed this illness in three out of sixty patients under CAPD. These patients had higher incidence of bacterial peritonitis. In the ascites high concentrations of PG E2 and Thromboxan B2 were observed. After treatment of the infection the concentrations fell down to normal values. Electronoptical observations from peritoneal biopsies showed a proliferation of myofibroblasts and extracellular lysosomes. It is known from these lysosomes that they are able to set free proteasis. These lead to degredation of fibrin and fibrinogen. These splits are mitogen to myofibroblasts. release from HIT cells could also be evoked by the sulphonylureas glibenclamide and tolbutamide and by an increase in concentration of extracellular K+ to 40 mmol/l. The content of cyclic AMP in HIT cells was increased modestly by glucose but not by an increase in extracellular K+. Forskolin elicited a 4-fold increase in cyclic AMP content. We conclude that HIT cells retain the essential features of the insulin secretory response of normal B cells and represent an important tool for further biochemical characterisation of the secretory system.

Topics: Adult; Bacterial Infections; Dinoprostone; Female; Fibrin; Humans; Intestinal Obstruction; Intestine, Small; Male; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Peritonitis; Prostaglandins E; Sclerosis; Thromboxane B2