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.

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

“…Consistent with this notion, in sheep, plasma UII concentrations are higher in the renal vein than in the renal artery (Charles et al, 2005), thus identifying the kidney as a source of circulating UII. In SHR, URP but not UII mRNA is elevated in kidney compared with WKY rats Forty and Ashton, 2013), suggesting a potential role for URP in spontaneous hypertension.…”

“…In the rat kidney, the UT gene is expressed in glomerular arterioles, thin ascending limbs, and inner medullary collecting ducts (Song et al, 2006a;Forty and Ashton, 2013). Quantitative receptor autoradiography confirms the presence of […”

“…The UT transcript is found in the kidney of human (Ames et al, 1999;Lehner et al, 2007), rat (Gartlon et al, 2001;Hirose et al, 2009;Mori et al, 2009;Forty and Ashton, 2013), and mouse (Lehner et al, 2007). In the rat kidney, the UT gene is expressed in glomerular arterioles, thin ascending limbs, and inner medullary collecting ducts (Song et al, 2006a;Forty and Ashton, 2013).…”

Urotensin-ⅡReceptor Antagonist SB-710411 Protects Rat Heart against Ischemia-Reperfusion Injury via RhoA/ROCK Pathway

“…Human U-II has been characterized as the most forceful arterial vasoconstrictors with 10–100 times more potent than endothelin-1 [ 5 ]. Large amount of data has demonstrated that the concentration of plasma human U-II is elevated in the cardiovascular diseases such as heart failure [ 6 ], atherosclerosis [ 7 ], hypertension [ 8 – 9 ], ischemia [ 10 ], chronic hypoxia [ 11 ]. Moreover, serum human U-II level was positively correlated with the degree of myocardium injury in a rat myocardial infarction model.…”

The Urotensin II System and Carotid Atherosclerosis: A Role in Vascular Calcification

“…Studies in mice have shown similar UII and URP expression in the nervous system, skeletal muscle, testes, vagina, and gall bladder, and differential expression in the seminal vesicles, heart, colon, and thymus (Dubessy et al, 2008 ). Another study of spontaneously hypertensive rats found elevated URP mRNA expression, suggesting a potential role for URP in spontaneous hypertension (Forty and Ashton, 2013 ). The differential cellular expression of URP in unstable vs. stable carotid atherosclerosis suggests that this may occur as either cause or effect in atherosclerotic disease and warrants further investigation.…”