Endothelin-1 (ET-1) is a potent renal and systemic vasoactive peptide. It acts through ETA and ETB receptors. We investigated density and subtype distribution of ET-1 receptors in hearts and kidneys of normotensive and hypertensive rats. Five groups of uninephrectomized Wistar rats were put on a low salt diet for six weeks. During this period, three groups of rats drank tap water and two groups received saline. One group of each regimen received DOCA subcutaneousely (1.6 mg/day). The fifth group of rats had the left renal artery clipped to induce 1K1C hypertension. At 6 weeks, mean arterial pressure (MAP) was recorded in conscious rats via a femoral artery catheter. Binding assays using 125I-ET-1 were carried out on membrane preparations in the presence and absence of the ETA receptor antagonist FR139317. On tap water, MAP was at 121.8±3.3 mmHg and DOCA or saline did not raise this MAP. On DOCA-salt and in 1K1C rats, MAP was increased to 154.5±5.8 mmHg (p<0.001) and 218.4±10.5 (p<0.001) mmHg, respectively. ET receptor subtypes were not equally expressed in the heart and the kidney: ETA was predominantly expressed in the heart, whereas ETB was predominant in the kidney. Both hypertensive models, the DOCA-salt and the 1K1C rats showed further significant changes: i) Cardiac weight index compared to controls of 2.49±0.06 mg/g was higher (p<0.001) at 3.89±0.10 and 4.86±0.18 mg/g in DOCA-salt and 1K1C hypertension, respectively, and kidney weight index compared to controls of 4.78±0.22 mg/g was higher at 10.10±0.54 mg/g in DOCA-salt (p<0.001) but tended to be below controls in 1K1C rats. ii) 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. iii) Plasma renin activity was decrased in DOCA-salt rats from 17±3 to 0.17±0.01 ng/ml/h and increased in 1K1C rats on low salt diet to 30±5 ng/ml/h (p<0.001). We conclude that upregulation of the ETB receptor mediating vasodilation and downregulation of the ETA receptor mediating vasoconstriction is compatible with a mainly renal counterregulatory effect of endothelin-1 to hypertension. This counterregulation may occur in both low and high renin models of hypertension. Am J Hypertens (2004) 17, 20A-21A; doi: 10.1016/j.amjhyper.2004.03.04
