Biomedical subjects

P-O Carlsson

Publications and source records attributed to P-O Carlsson.

6 recordsLinked to original sources

PubMed2003

Reactive oxygen species cause diabetes-induced decrease in renal oxygen tension.

AIMS/HYPOTHESIS: Augmented formation of reactive oxygen species (ROS) induced by hyperglycaemia has been suggested to contribute to the development of diabetic nephropathy. This study was designed to evaluate the influence of streptozotocin (STZ)-induced diabetes mellitus, as well as the effects of preventing excessive ROS formation by alpha-tocopherol treatment, on regional renal blood flow, oxygen tension and oxygen consumption in anaesthetized Wistar Furth rats. METHODS: Non-diabetic and STZ-diabetic rats were investigated after 4 weeks with or without dietary treatment with the radical scavenger DL-alpha-tocopherol (vitamin E, 5%). A laser-Doppler technique was used to measure regional renal blood flow, whilst oxygen tension and consumption were measured using Clark-type microelectrodes. RESULTS: Renal oxygen tension, but not renal blood flow, was lower throughout the renal parenchyma of diabetic rats when compared to non-diabetic control rats. The decrease in oxygen tension was most pronounced in the renal medulla. Renal cellular oxygen consumption was markedly increased in diabetic rats, predominantly in the medullary region. Diabetes increased lipid peroxidation and protein carbonylation in the renal medulla. Treatment with alpha-tocopherol throughout the course of diabetes prevented diabetes-induced disturbances in oxidative stress, oxygen tension and consumption. The diabetic animals had a renal hypertrophy and a glomerular hyperfiltration, which were unaffected by alpha-tocopherol treatment. CONCLUSIONS/INTERPRETATION: We conclude that oxidative stress occurs in kidneys of diabetic rats predominantly in the medullary region and relates to augmented oxygen consumption and impaired oxygen tension in the tissue.

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PubMed2003

Hypoglycaemia induces decreased islet blood perfusion mediated by the central nervous system in normal and Type 2 diabetic GK rats.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the effects of induced hypoglycaemia on pancreatic-islet blood flow in normal rats and in the GK rat, an animal model of Type 2 diabetes which normally has an increased islet blood perfusion. METHODS: A 50% reduction in blood glucose concentrations was achieved by intravenous administration of a rapidly acting insulin (15 IU/kg body weight). Blood flows were measured by a non-radioactive microsphere technique. RESULTS: A pronounced decrease in islet blood flow was observed in all animals, but preferentially in the Type 2 diabetic GK rats. When a similar dose of insulin was given to whole-pancreas transplanted rats only islet blood flow in the native pancreas was decreased, whereas that of the transplanted, i.e. denervated, pancreas was unchanged. Administration of 2-deoxy-D-glucose, which induces intracellular glucopenia especially in neurons, also decreased islet blood flow despite a systemic hyperglycaemia. CONCLUSION/INTERPRETATION: Hypoglycaemia leads to a preferential decrease in pancreatic-islet blood perfusion. The effect is probably mediated by the central nervous system, since 2-deoxy D-glucose-induced neuronal glucopenia caused a similar decrease in blood flow. The effects of islet blood flow are not likely to be mediated by nervous stimulation of the adrenal glands, with an associated release of catecholamines, because the transplanted pancreas was not affected by hypoglycaemia. The decreased islet blood perfusion could possibly diminish the output of insulin from the islets, thereby preventing a further decrease in blood glucose concentrations.

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PubMed2003

Altered response in renal blood flow and oxygen tension to contrast media in diabetic rats.

PURPOSE: To investigate the effect of the contrast medium (CM) iopromide on renal microcirculation and oxygen tension in non-diabetic control and streptozotocin-diabetic Wistar Furth rats. MATERIALS AND METHODS: Oxygen tension was measured with Clark-type microelectrodes and blood flow with laser-Doppler flow probes. In order to differentiate between an acutely increased blood glucose concentration and a long-term diabetic state, some of the non-diabetic control rats were intravenously infused with glucose. RESULTS: CM decreased the medullary oxygen tension in control (non-diabetic normoglycemic) rats ( approximately 35%) but not in diabetic rats. Medullary blood flow in control rats increased after CM administration and remained elevated, while it was unchanged in the diabetic rats. In response to CM, glucose-infused control rats responded similarly to control animals in medullary oxygen tension, but similarly to diabetic rats in medullary blood flow. Contrary to in control rats, medullary oxygen tension was unchanged in diabetic animals after CM administration. CONCLUSION: Streptozotocin-diabetic rats have an altered response to intravenous injection of the CM iopromide compared to non-diabetic rats. The unaltered medullary oxygen tension, seen in the diabetic group after injection of CM, suggests that non-hemodynamic mechanisms are responsible for the increased frequency of renal failure commonly seen among diabetic patients.

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PubMed2003

Et-A receptor antagonist BQ123 prevents radiocontrast media-induced renal medullary hypoxia.

PURPOSE: Renal vasoconstriction with resultant tissue hypoxia, especially in the renal medulla, has been suggested to play a role in contrast media (CM)-induced nephropathy. Endothelin (ET) is released into the blood stream following CM injection and has been proposed as a potential mediator through its vasoconstrictive properties. MATERIAL AND METHODS: To investigate the possible protective influence of ET-receptor antagonists against CM-induced reduction in renal function, we studied the effects of injection of iopromide with and without pretreatment with BQ123 (ET-A antagonist) or BQ788 (ET-B antagonist) on renal superficial cortical flow (CBF), outer medullary blood flow (OMBF) and outer medullary oxygen tension (pO2) in normal rats. RESULTS: Administration of CM (1600 mg I/kg b.w.) did not affect CBF in any of the groups. However, a transient decrease in OMBF occurred, which was unaffected by both BQ123 and BQ788. Also a transient decrease in outer medullary pO2 was induced by CM administration. The pO2 reduction was significantly smaller after pretreatment with BQ123, than after injection of CM alone or together with BQ788, and pO2 returned more rapidly to the control level. Neither receptor antagonist had an effect on CM-mediated increases in electrolyte excretion. CONCLUSION: In the normal rat, activation of ET-A receptors is partly involved in the depression of outer medullary pO2 caused by injection of iopromide. However, the decrease in OMBF after iopromide injection is not mediated by ET receptors. The beneficial effects of the ET-A receptor antagonist on CM-induced changes in outer medullary pO2 seem therefore not primarily mediated on the hemodynamic level but may rather involve tubular transport mechanisms.

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PubMed2002

Graft vascular function after transplantation of pancreatic islets.

Endogenous pancreatic islets have a dense glomerular-like angioarchitecture, which ensures an optimal delivery of oxygen and nutrients to the islet cells, provides signals from other cells in the body and disposes secreted hormones. Transplantation of isolated islets means that their vascular connection is interrupted. The islet grafts therefore depend upon endothelial cells and microvessels originating in the implantation organ for derivation of a new vascular system. A re-establishment of islet blood-flow occurs within 7-14 days after transplantation, mainly through vascular sprouting. The newly formed blood vessels acquire the morphological characteristics of those in endogenous islets. In intraportally transplanted islets to the liver, the islets become revascularized almost exclusively from tributaries to the hepatic artery. Exocrine contamination of the transplanted islets could hamper the revascularization process, whereas neither cryopreservation nor immunosuppressive drugs like cyclosporin, prednisolon and RS-61443 have any essential effects on the angiogenesis. Investigators have noticed improvements in islet graft survival and function by means of basic fibroblast growth factor (bFGF), acidic FGF and endothelial cell growth factor exposure of the grafts. The functional properties of transplanted islets are largely unknown, but evidence from experimental islet transplantation suggests that both the blood perfusion and the tissue oxygen tension of the grafted islets are chronically decreased, indicating an insufficient vascular system. In order to achieve optimal condition for survival and function of transplanted beta cells, it is important to ascertain whether impairments in vascular function are present also after clinical islet transplantations as well.

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PubMed2002

Unaltered oxygen tension in rat pancreatic islets despite dissociation of insulin release and islet blood flow.

The present study investigated the importance of a tightly regulated islet blood flow for an optimal oxygenation of the islet tissue during different demands for insulin release. Glucose and/or a non-specific nitric oxide synthase inhibitor (L-NNA) were infused intravenously in non-pretreated or vagotomized rats and the animals were subjected to measurements of islet blood flow, oxygen tension and serum insulin concentrations. Islet blood flow was measured using a non-radioactive microsphere technique, tissue oxygen tension was recorded with Clark microelectrodes and insulin concentrations were determined by enzyme-linked immunosorbent assay technique. Administration of L-NNA (0.3 mg kg(-1) min(-1)) for 10 min halved basal islet blood flow, but did not affect serum insulin concentrations. Glucose administration (10 mg kg(-1) min(-1)) induced a marked increase in islet blood flow, which could be prevented by vagotomy or L-NNA. The serum insulin concentrations increased in all glucose-infused animals. The islet tissue oxygen tension remained similar in all animals despite these interventions. Reasons other than oxygenation of the islet tissue must explain the normally existing tight regulation of islet blood flow.

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