Enhanced renal sensitivity of the spontaneously hypertensive rat to urotensin II.
Urotensin II (UII) has been implicated widely in cardiovascular disease. The mechanism(s) through which it contributes to elevated blood pressure is unknown, but its emerging role as a regulator of mammalian renal function suggests that the kidney might be involved. The aim of this study was to determine the effect of UII on renal function in the spontaneously hypertensive rat (SHR). UII infusion (6 pmol.min(-1).100 g body wt(-1)) in anesthetized SHR and control Wistar-Kyoto (WKY) rats produced marked reductions in glomerular filtration rate (DeltaGFR WKY, n=7, -0.3+/-0.1 vs. SHR, n=7, -0.6+/-0.1 ml.min(-1).100 g body wt(-1), P=0.03), urine flow, and sodium excretion rates, which were greater in SHR by comparison with WKY rats. WKY rats also showed an increase in fractional excretion of sodium (DeltaFE(Na); +0.6+/-0.1%, P=0.02) in contrast to SHR in which no such change was observed (DeltaFE(Na) -0.6+/-0.2%). Blockade of the UII receptor (UT), and thus endogenous UII activity, with urantide evoked an increase in GFR which was greater in SHR (+0.3+/-0.1) compared with WKY rats (+0.1+/-0.1 ml.min(-1).100 g body wt(-1), P=0.04) and was accompanied by a diuresis and natriuresis. UII and UT mRNA expression were greater in the renal medulla than the cortex of both strains; however, expression levels were up to threefold higher in SHR tissue. SHR are more sensitive than WKY to UII, which acts primarily to lower GFR thus favoring salt retention in this model of hypertension.
Abdel-Razik
Alaa E S
AE
Faculty of Life Sciences, University of Manchester, 1.124 Stopford Bldg., Oxford Road, Manchester M13 9PT, UK.
Balment
Richard J
RJ
Ashton
Nick
N
D000818:Animals; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D006977:Hypertension, Renal / Q000378:metabolism* / Q000503:physiopathology*; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000502:physiology; D007679:Kidney Medulla / Q000502:physiology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012964:Sodium / Q000652:urine; D014556:Urine; D014579:Urotensins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D010446:Peptide Fragments; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C473142:Uts2r protein, rat; C492079:urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-; C029677:urotensin II; D012964:Sodium