dinoprost and Hydronephrosis

Hydronephrosis causes renal dysfunction and salt-sensitive hypertension, which is associated with nitric oxide deficiency and abnormal tubuloglomerular feedback (TGF) response. We investigated the role of oxidative stress for salt sensitivity and for hypertension in hydronephrosis. Hydronephrosis was induced in superoxide dismutase 1-transgenic (SOD1-tg), SOD1-deficient (SOD1-ko), and wild-type mice and in rats. In mice, telemetric measurements were performed during normal (0.7% NaCl) and high-sodium (4% NaCl) diets and with chronic tempol supplementation. The 8-iso-prostaglandin-F(2alpha) (F2-IsoPs) and protein excretion profiles and renal histology were investigated. The acute effects of tempol on blood pressure and TGF were studied in rats. In hydronephrosis, wild-type mice developed salt-sensitive hypertension (114 +/- 1 to 120 +/- 2 mmHg), which was augmented in SOD1-ko (125 +/- 3 to 135 +/- 4 mmHg) but abolished in SOD1-tg (109 +/- 3 to 108 +/- 3 mmHg). SOD1-ko controls displayed salt-sensitive blood pressure (108 +/- 1 to 115 +/- 2 mmHg), which was not found in wild types or SOD1-tg. Chronic tempol treatment reduced blood pressure in SOD1-ko controls (-7 mmHg) and in hydronephrotic wild-type (-8 mmHg) and SOD1-ko mice (-16 mmHg), but had no effect on blood pressure in wild-type or SOD1-tg controls. SOD1-ko controls and hydronephrotic wild-type and SOD1-ko mice exhibited increased fluid excretion associated with increased F2-IsoPs and protein excretion. The renal histopathological changes found in hydronephrotic wild-type were augmented in SOD1-ko and diminished in SOD-tg mice. Tempol attenuated blood pressure and normalized TGF response in hydronephrosis [DeltaP(SF): 15.2 +/- 1.2 to 9.1 +/- 0.6 mmHg, turning point: 14.3 +/- 0.8 to 19.7 +/- 1.4 nl/min]. Oxidative stress due to SOD1 deficiency causes salt sensitivity and plays a pivotal role for the development of hypertension in hydronephrosis. Increased superoxide formation may enhance TGF response and thereby contribute to hypertension.

Topics: Animals; Antioxidants; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cyclic N-Oxides; Dinoprost; Disease Models, Animal; Feedback, Physiological; Female; Hydronephrosis; Hypertension; Infusions, Intravenous; Kidney; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Proteinuria; Rats; Rats, Sprague-Dawley; Sodium Chloride, Dietary; Spin Labels; Superoxide Dismutase; Superoxide Dismutase-1; Telemetry; Urodynamics

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Child; Child, Preschool; Chronic Disease; Dinoprost; Dinoprostone; Female; Humans; Hydronephrosis; Male; Prostaglandins; Pyelonephritis; Reference Values; Renin; Sodium; Thromboxane B2; Vesico-Ureteral Reflux

A case of familial central diabetes insipidus and dilatation of the urinary tract is reported. Administration of desmopressin for 1 year improved urinary tract dilatation with a concomitant reduction in urine volume. Urinary cyclic adenosine monophosphate and prostaglandin E2 excretion increased after treatment.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Cyclic AMP; Deamino Arginine Vasopressin; Diabetes Insipidus; Dinoprost; Dinoprostone; Humans; Hydronephrosis; Male; Thromboxane B2; Urine

Regional localization of the exaggerated prostaglandin E2 (PGE2) synthesis caused by hydronephrosis was studied in unilateral ureteral ligated rabbits. The renal distribution of PGE2 production was compared in the hydronephrotic and contralateral kidneys. Basal and bradykinin-stimulated PGE2 synthesis were increased in cortical and medullary slices of the hydronephrotic kidneys. Contralateral (control) cortical slices produced very low levels of PGE2 and were insensitive to stimulation by bradykinin (BK). The hydronephrotic cortex produced 10 times more PGE2 than the contralateral cortex and responded to BK stimulation with increased PGE2 synthesis. Cortical slices from the hydronephrotic kidney exhibited a time-dependent increase in PGE2 release, presumably as a result of new protein synthesis. The division of the hydronephrotic cortex into outer and inner regions revealed that the inner cortex produced more PGE2 than the outer cortex. A similar division of the hydronephrotic medulla showed that the inner medulla produced slightly greater amounts of PGE2 than the outer medulla. The present study demonstrates that hydronephrosis causes increases in prostaglandin synthesis throughout the kidney. We suggest from these results and other studies that a possible explanation for this finding is the involvement of the collecting duct system in this response. The gradient of PGE2 production detected in the cortex may have a very significant role in the control of renal hemodynamics and could provide an explanation for the large decrease in blood flow to the inner cortex caused by indomethacin treatment.

Topics: Animals; Aspirin; Bradykinin; Cycloheximide; Dinoprost; Hydronephrosis; Kidney; Kidney Cortex; Kidney Medulla; Male; Prostaglandins F; Rabbits; Time Factors; Tissue Distribution