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(Hypertension. 2001;37:275.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Renal Endothelin ET_A/ET_B Receptor Imbalance Differentiates Salt-Sensitive From Salt-Resistant Spontaneous Hypertension

Lars Rothermund; Susanne Luckert; Peter Koßmehl; Martin Paul; Reinhold Kreutz

From the Institut für Klinische Pharmakologie und Toxikologie (L.R., S.L., P.K., M.P., R.K.), Medizinische Klinik IV Nephrologie (R.K.), Benjamin Franklin Hospital, Freie Universität Berlin, Berlin, Germany.

Correspondence to PD Dr Reinhold Kreutz, Department of Clinical Pharmacology, Benjamin Franklin Klinikum, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail Kreutz{at}medizin.fu-berlin.de Dr Rothermund’s present address is Medizinische Klinik mit Schwerpunkt Nephrologie der Charité Campus Mitte, Humboldt Universität zu Berlin, 10117 Berlin, Germany.

It is unclear why a subgroup of patients with essential hypertension develop salt-sensitive hypertension with progression of target organ damage over time. We evaluated the role of the renal endothelin (ET) system in the stroke-prone spontaneously hypertensive rat (SHRSP) model of salt-sensitive spontaneous hypertension (SS-SH) compared with the spontaneously hypertensive rat (SHR) model of salt-resistant spontaneous hypertension (SR-SH). Both strains were studied after either sham-operation on a normal diet (Sham) or after unilateral nephrectomy and high NaCl loading (NX-NaCl) with 4% NaCl in diet for 6 weeks (n=10, respectively). Systolic blood pressure (SBP) increased only in SHRSP-NX-NaCl compared with SHRSP-Sham (250±6 versus 172±5 mm Hg, P<0.0001). SBP remained unchanged in SHR-NX-NaCl compared with SHR-Sham. In SHRSP-NX-NaCl animals, urinary albumin and ET-1 excretion, renal ET-1 mRNA expression, glomerulosclerosis index, and tubulointerstitial damage index were elevated compared with SHRSP-Sham (P<0.05, respectively), whereas no significant changes were found in SHR after NX-NaCl. Urinary sodium excretion (U_Na⁺) was significantly reduced by 38% in SHRSP-NX-NaCl compared with SHR-NX-NaCl (P<0.005, respectively). SHR animals showed a similar increase in both renal ET_A and ET_B receptor densities after NX-NaCl (2.2-fold, P<0.05). In contrast, SHRSP-NX-NaCl developed a significantly more pronounced increase in ET_A compared with ET_B binding (4.7-fold versus 2.4-fold, P<0.05, compared with SHRSP-Sham, respectively), resulting in a significant 2.1-fold increase in ET_A/ET_B receptor ratio only in the SHRSP-NX-NaCl (P<0.05). Thus, activation of the renal ET system together with an increased ET_A/ET_B receptor ratio may contribute to the development and progression of SS-SH.

Key Words: sodium • hypertension, sodium-dependent • endothelin • receptors, endothelin • rats, spontaneously hypertensive • rats, stroke-prone SHR

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