Renal endothelin receptor type B upregulation in rats with low or high renin hypertension.
OBJECTIVE
To evaluate the role of endothelin-1 (ET-1) in hypertension, we investigated density and distribution of ETA and ETB receptors in hearts and kidneys of deoxycorticosterone acetate (DOCA)-salt and 1 kidney -- 1 clip (1K1C) hypertensive rats.


METHODS
Five groups of uninephrectomized Wistar rats were put on a low salt diet. Three groups of rats drank tap water and two groups received saline. One group of each regimen received DOCA subcutaneously and two corresponding groups without DOCA served as controls. The fifth group of rats had the renal artery clipped to induce 1K1C hypertension. At 6 weeks, mean arterial pressure (MAP) was recorded and membrane binding assays using 125I-ET-1 were carried out.


RESULTS
MAP was increased from control 122 +/- 3 to 155 +/- 6 and 218 +/- 11 mmHg in DOCA-salt and 1K1C rats, respectively, and cardiac weight index was increased. ETA receptors were predominantly expressed in the heart, whereas ETB receptors were predominant in the kidney. In the kidneys, the density of the ETB receptor subtype was upregulated in DOCA-salt and 1K1C rats from 160 +/- 8 to 217 +/- 12 and 190 +/- 2 fmol/mg (P < 0.05), respectively, and ETA tended to be downregulated (P = 0.057). Plasma renin activity was decreased in DOCA-salt rats from 17 +/- 3 to 0.17 +/- 0.01 ng/ml per h and increased in 1K1C rats on low salt diet to 30 +/- 5 ng/ml per h.


CONCLUSIONS
Since ETB is the predominant endothelin receptor in the kidneys, upregulation of the ETB receptor mediating vasodilation and downregulation of the ETA receptor mediating vasoconstriction would be compatible with a mainly renal counter-regulatory effect of endothelin-1 to hypertension. Both low and high renin models of hypertension may be affected.
Division of Hypertension and Vascular Medicine, University Hospital, CH-1011 Lausanne, Switzerland. noureddine.brakch@chuv.hospvd.ch
Noureddine
N
Brakch
Saad
S
Abdel-Sayed
Flore
F
Allemandou
Qing
Q
Wang
Jean F
JF
Aubert
Hans R
HR
Brunner
Juerg
J
Nussberger
D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D003900:Desoxycorticosterone / Q000031:analogs & derivatives*; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology; D006339:Heart Rate; D006977:Hypertension, Renal / Q000139:chemically induced / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism*; D012083:Renin / Q000378:metabolism*; D012965:Sodium Chloride; D015854:Up-Regulation
D019332:Endothelin-1; D007457:Iodine Radioisotopes; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D012083:Renin