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.

Hyaluronan content in the kidney in different states of body negatively charged linear glucosaminoglycan, made up hydration. of repeating disaccharide units of D-glucuronic acid and Background. Growing evidence suggests that the interstitial N-acetyl-D-glucosamine [1]. HA is formed at the inner hyaluronan (HA) content is a determinant of the fluid exchange surface of the plasma membrane and is extruded into barrier in tissues through its high resistance to water flow. This the extracellular matrix [2]. It is of major importance in study addressed the possible involvement of renal papillary HA in water balance regulation. many biological processes. Biological roles of HA in-Methods. In anesthetized rats during different states of renal clude stabilization of the loose connective tissue, maintewater handling (euvolemia, water diuresis, antidiuresis), in denance of water and protein homeostasis, protection of sert rodents, and in Brattleboro rats (diabetes insipidus) with cells from potentially harmful effects of other cells and a hereditary difference in water handling, regional renal HA and water contents were measured. microorganisms, and modulation of the inflammatory Results. The intrarenal HA distribution is heterogeneous, reaction [1, 3, 4]. with 100 times larger amounts in the papilla than in the cortex.

Dopamine is a natriuretic hormone that is abundantly synthesized in the kidney and is involved in sodium homeostasis. It is metabolized by monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) to form 3-methoxytyramine and dihydroxyphenylacetic acid (DOPAC) and finally homovanillic acid (HVA). In order to investigate whether dopamine metabolism is involved in renal sodium regulation, we tested the renal effects of the nitrocatechol entacapone (COMT inhibitor), in comparison with those of the pyridine derivative CGP 28014, in the anaesthetized rat. Entacapone injection resulted in a more than 5-fold increase in sodium excretion, while the renal excretion of dopamine only transiently increased by 20%. DOPAC excretion showed a more than 2-fold increase which persisted throughout the study. Pretreatment with the selective dopamine DA1-receptor antagonist SCH23390 reduced the entacapone-induced natriuretic response by 69%. Glomerular filtration rate (GFR) and mean arterial blood pressure (MAP) remained unchanged. Injection of CGP 28014 did not produce a natriuretic response; nevertheless, both dopamine and DOPAC excretion increased by 78% and more than 2-fold, respectively. GFR and MAP remained unchanged. In conclusion, COMT inhibition using entacapone results in a mainly DA1 receptor mediated natriuresis involving inhibition of tubular transport processes, supporting a role for dopamine metabolism in sodium homeostasis. Although CGP 28014 increases the renal excretion of both dopamine and DOPAC it does not affect renal sodium handling indicating a different mechanism of action.

The intrarenal natriuretic hormone dopamine (DA) is metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). We have previously shown that inhibition of COMT by entacapone results in a potent D1-like receptor-mediated natriuretic response. The present study was performed using anaesthetized rats to compare the importance of MAO and COMT in DA-mediated natriuresis by use of the MAO inhibitor phenelzine. Urinary sodium and DA excretion remained unchanged after MAO inhibition, while excretion of the main metabolite dihydroxyphenylacetic acid (DOPAC) decreased by 55%. The response was unaltered if 5-hydroxytryptamine receptors (5-HT1A) were blocked during MAO inhibition. We also investigated the specific renal activities of MAO and COMT in rat renal cortex during DA-influenced natriuresis. Specific COMT activity in the renal cortex was reduced by 13% after isotonic sodium loading (5% of body mass) whereas renal MAO-A and MAO-B activities remained unaltered. Furthermore, preliminary data obtained from spontaneously hypertensive rats, whose basal urinary DA excretion is higher than that of normotensive Wistar-Kyoto rats, show a tendency for renal COMT activity to be lower. It is concluded that MAOinhibition by phenelzine does not alter 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 MAO is less important than COMT in regulating DA-mediated natriuresis in the rat kidney.