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The urotensin system is up-regulated in the pre-hypertensive spontaneously hypertensive rat.

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.

SUBMITTER: Forty EJ

PROVIDER: S-EPMC3855556 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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The urotensin system is up-regulated in the pre-hypertensive spontaneously hypertensive rat.

Forty Ellen J EJ Ashton Nick N

PloS one 20131205 12

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 ...[more]

PMID: 24340095

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Project description:BackgroundSeveral members of connexin family of transmembrane proteins were previously implicated in distinct metabolic conditions. In this study we aimed to determine the effects of complete and heterozygous form of connexin50 gene (Gja8) mutation L7Q on metabolic profile and oxidative stress parameters in spontaneously hypertensive inbred rat strain (SHR).MethodsAdult, standard chow-fed male rats of SHR, heterozygous SHR-Dca+/- and SHR-Dca-/- coisogenic strains were used. At the age of 4 months, dexamethasone (2.6 μg/ml) was administered in the drinking water for three days. The lipidemic profile (cholesterol and triacylglycerol concentration in 20 lipoprotein fractions, chylomicron, VLDL, LDL and HDL particle sizes) together with 33 cytokines and hormones in serum and several oxidative stress parameters in plasma, liver, kidney and heart were assessed.ResultsSHR and SHR-Dca-/- rats had similar concentrations of triacylglycerols and cholesterol in all major lipoprotein fractions. The heterozygotes reached significantly highest levels of total (SHR-Dca+/-: 51.3 ± 7.2 vs. SHR: 34.5 ± 2.4 and SHR-Dca-/-: 34.4 ± 2.5 mg/dl, p = 0.026), chylomicron and VLDL triacylglycerols. The heterozygotes showed significantly lowest values of HDL cholesterol (40.9 ± 2.3 mg/dl) compared both to SHR (51.8 ± 2.2 mg/dl) and SHR-Dca-/- (48.6 ± 2.7 mg/dl). Total and LDL cholesterol in SHR-Dca+/- was lower compared to SHR. Glucose tolerance was improved and insulin concentrations were lowest in SHR-Dca-/- (1.11 ± 0.20 pg/ml) in comparison with both SHR (2.32 ± 0.49 pg/ml) and SHR-Dca+/- (3.04 ± 0.21 pg/ml). The heterozygous rats showed profile suggestive of increased oxidative stress as well as highest serum concentrations of several pro-inflammatory cytokines including interleukins 6, 12, 17, 18 and tumor necrosis factor alpha.ConclusionsOur results demonstrate that connexin50 mutation in heterozygous state affects significantly the lipid profile and the oxidative stress parameters in the spontaneously hypertensive rat strain.

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The urotensin system is up-regulated in the pre-hypertensive spontaneously hypertensive rat.

Publications

The urotensin system is up-regulated in the pre-hypertensive spontaneously hypertensive rat.

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