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- Hansell, Peter, et al.
(författare)
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Hyaluronan content in the kidney in different states of body hydration
- 2000
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Ingår i: Kidney International. - 0085-2538 .- 1523-1755. ; 58:5, s. 2061-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Growing evidence suggests that the interstitial hyaluronan (HA) content is a determinant of the fluid exchange barrier in tissues through its high resistance to water flow. This study addressed the possible involvement of renal papillary HA in water balance regulation. METHODS: In anesthetized rats during different states of renal water handling (euvolemia, water diuresis, antidiuresis), in desert rodents, and in Brattleboro rats (diabetes insipidus) with a hereditary difference in water handling, regional renal HA and water contents were measured. RESULTS: The intrarenal HA distribution is heterogeneous, with 100 times larger amounts in the papilla than in the cortex. Compared with control rats, two hours of water diuresis increased the papillary HA content by 48% and that in the outer medulla by 52%, leaving the cortex unaffected. After 24 hours of water deprivation, papillary HA was decreased by 17%, while outer medullary HA remained unchanged. In gerbils, papillary and outer medullary HA contents were only 25 and 13%, respectively, of those in normal rats, while the cortical content was similar. In Brattleboro rats, the outer medullary HA content was significantly higher (285%) than in the normal rat, while the papillary content was similar. Generally, papillary HA was positively correlated to water content but was inversely related to urine osmolality. CONCLUSIONS: The amount of renal papillary HA changes in response to water balance of the organism. When excess water needs to be excreted, increased papillary interstitial HA could antagonize water reabsorption. The opposite occurs during water conservation. HA may play a role in renal water handling by affecting physicochemical characteristics of the papillary interstitial matrix and influencing the interstitial hydrostatic pressure, thereby determining interstitial water diffusion.
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| 3. |
- Odlind, Cecilia
(författare)
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The Role of Dopamine-Metabolising Enzymes in Renal Sodium Handling. An Experimental Study in vivo
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dopamine (DA) has been shown to act as an intrarenal natriuretic hormone and defects in the renal DA system have been associated with some forms of hypertension. How the DA activity is upregulated durin- increased sodium intake is, however, unknown. The present study addressed some aspects of the regulation and execution of DA-mediated natriuresis, with the main focus on the role of the DA-metabolising enzyme catechol-O-methyltransferase (COMT). COMT inhibition results in DA-induced natriuresis. The natriuretic response is mediated via the D1-like receptor and not the D2-like receptor and does not involve changes in renal haemodynamics, pointing to an effect on tubular sodium transport. MAO inhibition does not after sodium excretion. Furthermore, specific renal cortical COMT activity is reduced during partly D1-like receptor-mediated natriuresis, whereas MAO activity remains unchanged. The results suggest that the importance of MAO is negligible compared to COMT in regulating DA- mediated natriuresis in the rat. Systemic administration of a DA precursor only results in a modest increase in urinary sodium excretion in spite of a large increase in urinary DA excretion. These results indicate that DA metabolism is important in sodium homeostasis and that intrarenal DA activity is more likely regulated via DA metabolism and not primarily through a change in the systemic availability of the DA precursor. The natriuretic and haemodynamic effects of an elevation in DA activity were shown to depend on the route by which the elevation occurred. Intrarenally produced DA does not influence haemodynamics, whereas a DA agonist given systematically elicits an increase in cortical and outer medullary blood flow via vascular D1-like receptors. Cortical and outer medullary oxygen tension was not measurably altered during DA- induced natriuresis. In genetically modified mice it was shown that a reduced or absent COMT activity results in an inability to increase the renal DA activity and to produce normal natriuresis in response to sodium loading. In summary, the results from the present study suggests that COMT activity in the kidney plays an important role in the DA-mediated regulation of renal sodium excretion in response to sodium loading in rats and mice.
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