Abstract
Urotensin II (UII) concentrations are raised both in humans with hypertension and in spontaneously hypertensive rats (SHR). Since the urotensin system acts to regulate glomerular filtration in the kidney it may play a greater role in the pre-hypertensive SHR in which renal dysfunction is known to precede the onset of severe hypertension. This study aimed to determine the renal actions and expression of the urotensin system in the young SHR. Intravenous rat UII (6 pmol. min-1. 100 g body weight-1) had no significant effect on GFR; however urotensin-related peptide (URP) reduced GFR (P<0.05) in 4-5 week old SHR. Administration of the UT antagonist SB-706375 evoked marked increases in GFR (baseline 0.38 ± 0.07 vs antagonist 0.76 ± 0.05 ml. min-1. 100 g body weight-1, P<0.05), urine flow and sodium excretion (baseline 2.5 ± 0.4 vs antagonist 9.1 ± 2.1 µmol. min-1. 100 g body weight-1, P<0.05) in the SHR. Normotensive Wistar-Kyoto rats showed little response to UT antagonism. Quantitative RT-PCR showed that neither UII nor UT mRNA expression differed between the kidneys of young SHR and WKY rats; however expression of URP was 4-fold higher in the SHR kidney. Renal transcriptional up-regulation indicates that URP is the major UT ligand in young SHR and WKY rats. Enhanced tonic UT activation may contribute to known renal dysfunction in pre-hypertensive SHR.
Highlights
Urotensin II (UII) and its receptor, UT, are expressed abundantly in the kidneys of humans [1], rats [2] and other mammals [3]
In common with adult spontaneously hypertensive rats (SHR) [13], activation of UT by endogenous urotensin peptides has a greater impact upon renal haemodynamics in the young SHR with moderately elevated blood pressure compared with WKY rats
The pronounced natriuresis and diuresis that accompanied UT antagonism in the young SHR suggests that tonic activation of UT by urotensin peptides may contribute to the retention of sodium and water which precedes the rapid elevation in blood pressure and onset of hypertension as the SHR matures [16]
Summary
Urotensin II (UII) and its receptor, UT, are expressed abundantly in the kidneys of humans [1], rats [2] and other mammals [3]. Urotensin-related peptide (URP), an homologous alternative ligand with a similar affinity and potency to UII at UT [4], is expressed in both human [4] and rat [2] kidneys. UT activation leads to a reduction in urinary sodium and water loss, as a result of a decrease in GFR. The actions of UII are dose-related, with sodium loss enhanced at low doses and sodium retention stimulated at higher doses [5]. Up-regulation of the renal urotensin system is likely to lead to sodium retention and an increase in systemic blood pressure
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