title: Connecting tubule glomerular feedback in hypertension.
abstract: In Dahl salt-sensitive rats (Dahl SS), glomerular capillary pressure increases in response to high salt intake and this is accompanied by significant glomerular injury compared with spontaneously hypertensive rats with similar blood pressure. Glomerular capillary pressure is controlled mainly by afferent arteriolar resistance, which is regulated by the vasoconstrictor tubule glomerular feedback (TGF) and the vasodilator connecting TGF (CTGF). We hypothesized that Dahl SS have a decreased TGF response and enhanced TGF resetting compared with spontaneously hypertensive rats, and that these differences are attributable in part to an increase in CTGF. In vivo, using micropuncture we measured stop-flow pressure (a surrogate of glomerular capillary pressure). TGF was calculated as the maximal decrease in stop-flow pressure caused by increasing nephron perfusion, TGF resetting as the attenuation in TGF induced by high salt diet, and CTGF as the difference in TGF response before and during CTGF inhibition with benzamil. Compared with spontaneously hypertensive rats, Dahl SS had (1) lower TGF responses in normal (6.6±0.1 versus 11.0±0.2 mm Hg; P<0.001) and high-salt diets (3.3±0.1 versus 10.1±0.3 mm Hg; P<0.001), (2) greater TGF resetting (3.3±0.1 versus 1.0±0.3 mm Hg; P<0.001), and (3) greater CTGF (3.4±0.4 versus 1.2±0.1 mm Hg; P<0.001). We conclude that Dahl SS have lower TGF and greater CTGF than spontaneously hypertensive rats, and that CTGF antagonizes TGF. Furthermore, CTGF is enhanced by a high-salt diet and contributes significantly to TGF resetting. Our findings may explain in part the increase in vasodilatation, glomerular capillary pressure, and glomerular damage in SS hypertension during high salt intake.
authors: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI 48202. ocarret1@hfhs.org.
authors: Hong
authors: H
authors: Wang
authors: Martin A
authors: MA
authors: D'Ambrosio
authors: Jeffrey L
authors: JL
authors: Garvin
authors: Yilin
authors: Y
authors: Ren
authors: Oscar A
authors: OA
authors: Carretero
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D009399:Nephrons / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D020303:Rats, Inbred Dahl; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: C013407:benzamil; D000584:Amiloride
keywords: CTGF; Dahl salt-sensitive rats; TGF; benzamil; rats, inbred SHR
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