urografin-76 and Disease-Models--Animal

The systemic administration of hypertonic solutions may activate the adrenergic system, thus triggering vasomotor reactions that may result in renal failure. In this study, the effects of diatrizoate meglumine sodium radiocontrast agent Hypaque-76 on systolic blood pressure (BP) and renal damage were determined in male spontaneously hypertensive (SH) rats and Wistar Kyoto (WKY) rats under adrenergic blockade.. The systolic BP was measured in ketamine-anesthetized male SH and WKY rats after administration of saline solution, radiocontrast, or endothelin during adrenergic blockade with phentolamine. Then the left kidney was removed and examined histologically.. The fall in systolic BP after phentolamine was not influenced by saline solution or radiocontrast in WKY rats but was restored partially by radiocontrast in SH rats. Endothelin produced an elevation in BP toward baseline levels in both strains. Only moderate renal damage was observed in the kidneys of WKY rats given radiocontrast or endothelin, but very severe damage was produced by these agents in SH rats.. Adrenergic blockade with phentolamine did not prevent the elevation in systolic BP in SH rats by radiocontrast or by endothelin in SH and WKY rats, nor did it protect against renal damage by radiocontrast or by endothelin in SH rats.

Topics: Adrenergic alpha-Antagonists; Animals; Blood Pressure; Contrast Media; Diatrizoate; Diatrizoate Meglumine; Disease Models, Animal; Drug Combinations; Endothelins; Hypertension; Kidney; Male; Phentolamine; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sympathetic Nervous System

We describe here a new procedure designed to enable reproducible sustained erection in a canine model. In 10 dogs, an end-to-side arteriovenous fistula was created between the inferior epigastric artery and deep dorsal vein. A chronic skin tunnel was created at the penile base. Blood flow, intracavernosal pressure and intraspongiosal pressure and blood gases were measured initially and 3 months later. Cuff application for 30 minutes was used daily. At 3 months, animals were sacrificed and biopsies obtained. Physiologic and histological parameters of erectile structures remained unchanged. Intracavernosal and intraspongiosal pressures increased to 33.7 +/- 6.7 mm Hg and 25.3 +/- 12.2 mm Hg (from 8.0 +/- 2.9 and 6.0 +/- 3.6 mm Hg) after cuff application. We conclude that sustained erections are feasible. This procedure appears safe for human trials.

Topics: Anastomosis, Surgical; Animals; Arteriovenous Shunt, Surgical; Biopsy; Blood Pressure; Carbon Dioxide; Constriction; Contrast Media; Dermatologic Surgical Procedures; Diatrizoate; Diatrizoate Meglumine; Disease Models, Animal; Dogs; Drug Combinations; Epigastric Arteries; Erectile Dysfunction; Feasibility Studies; Follow-Up Studies; Humans; Male; Oxygen; Penile Erection; Penis; Pressure; Radiography; Regional Blood Flow; Reproducibility of Results; Safety; Scrotum; Vascular Patency; Veins

In the present study we investigated the role of endothelin and AT II in radiocontrast nephropathy induced in rats with reduced renal mass (70-75%). Thirty-five male Wistar albino rats weighing between 280 and 400 g were anaesthetized with ketamine (130 mg/kg b.w.) and right total, left 50% nephrectomy were performed. After this operation, the rats were kept under observation for six to eight weeks and then they were randomly separated into three groups. Group I rats were infused with 8.9 ml/kg (or 2.9 g of iodine/kg body weight) Na diatrizoate (Urovision, 1,500 mosm/kg). Group II rats were infused with 0.9% NaCl in an equal volume with the radiocontrast material. Group III rats were given 4.5% NaCl that had the same volume and osmolality as the radiocontrast material. Two hours after the drug infusions, blood and accumulated urine samples were collected from all the rats and tested for endothelin, AT II, BUN, creatinine, uric acid, electrolytes, calcium and phosphorus. We found that the plasma endothelin levels in Group I (77.64 +/- 29.62 pg/ml) were significantly higher than in Group II (20.52 +/- 5.83 pg/ml) and Group III (15.04 +/- 5.15 pg/ml) (t = 8.34 and t = 9.14, respectively, p < 0.001). Therefore elevation in circulating endothelin might have been an additional factor leading to the radiocontrast-induced nephrotoxicity.

Topics: Angiotensin II; Animals; Blood Urea Nitrogen; Contrast Media; Diatrizoate; Diatrizoate Meglumine; Disease Models, Animal; Drug Combinations; Endothelins; Infusions, Intravenous; Iodine; Kidney; Kidney Diseases; Male; Nephrectomy; Radioimmunoassay; Radioisotopes; Random Allocation; Rats; Rats, Wistar; Reference Values

The male spontaneously hypertensive rat (SHR), as it ages, suffers many of the renal and cardiovascular complications that are recognized in humans as risk factors for radiocontrast (RC) agent induced renal failure (RF). Knowledge of this led us to test this strain of rats as a small animal model for RC-induced renal failure (RC-RF). Functional studies demonstrated a significant fall in GFR in the recovery period after RC administration. In addition, histopathologic evaluation of the kidneys was done in this study. Our results are based on assigning separate scale values to the histopathological evaluation of the (a) glomeruli, (b) tubules, (c) interstitium, and (d) arteries and arterioles of the kidneys. Saline (S) was administered to one group and the RC agent Hypaque-76 (diatrizoate meglumine sodium) to paired groups of 5-, 8-, 10-, 12-, and 14-month-old male SHR. The results indicated that younger animals (5 and 8 months old) were resistant to the nephrotoxic effects of the RC, but developed susceptibility at 10 months of age, when spontaneous renal pathology became manifest. Both spontaneous renal pathology and RC-induced renal damage (RC-RD) increased as the animals aged. In addition, when the administered dose of RC was repeated after a short interval of only 6 h, the degree of RC-RD increased greatly. In parallel control studies of the influence of gender and strain on the response to RC in 12-month-old rats, neither hypertensive female SHR nor male normotensive Wistar-Kyoto (WKY) rats demonstrated significant spontaneous renal pathology or the marked susceptibility to RC nephrotoxicity shown by their male SHR counterparts. This small animal model for RC-RD, the mature male SHR, has the distinct advantage that risk factors for RC-RD, similar to those characterized in humans for RC-RF, develop spontaneously without requiring any special treatment or surgical intervention.

Topics: Age Factors; Animals; Contrast Media; Diatrizoate; Diatrizoate Meglumine; Disease Models, Animal; Drug Combinations; Female; Glomerular Filtration Rate; Kidney Glomerulus; Kidney Tubules; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renal Artery; Renal Insufficiency; Risk Factors; Sex Factors; Species Specificity