Thiazide diuretic receptors in spontaneously hypertensive rats and 2-kidney 1-clip hypertensive rats.
Thiazide diuretic receptor density was assessed in kidneys from spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats by measuring hydroflumethiazide-displaceable 3H-metolazone binding to renal membranes in vitro. Renal thiazide receptor density was not significantly different in 4 week old SHR and WKY rats, but was significantly increased by 20%-40% in 14-49 week old SHRs compared to WKY rats. Affinity of receptors for 3H-metolazone did not differ between SHRs and WKY rats at any age. In WKY rats with 2 kidney-1 clip (2K-1C) hypertension, thiazide receptor density was not significantly different in either clipped or unclipped kidneys from sham-operated controls. Thus, increased renal thiazide receptor density occurs in SHRs along with the development of hypertension and does not appear to be secondary to increased renal perfusion pressure. This increase may reflect altered hormonal or ionic input to the distal tubule and may contribute to elevated sodium reabsorption in this segment in the SHR.
Beaumont
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K
Department of Medicine, School of Medicine, University of California, San Diego, La Jolla 92093.
Vaughn
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Casto
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Printz
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Fanestil
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D000818:Animals; D002352:Carrier Proteins; D005260:Female; D006973:Hypertension / Q000378:metabolism*; D006978:Hypertension, Renovascular / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008788:Metolazone / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011955:Receptors, Drug / Q000378:metabolism*; D012737:Sex Factors; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters
D002352:Carrier Proteins; D011955:Receptors, Drug; C578876:Slc12a3 protein, rat; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor; D008788:Metolazone