We observed that heterozygous knockout (+/−, KO) of either endothelin-A-(ET A) or-B-(ET B) receptors significantly reduced the pressor responses to systemically administered endothelin-1 (ET-1) in ET A or ET B (+/−) KO mice when compared to wild-type (WT) mice (data not shown). Also, we observed that basal mean arterial pressure (MAP) is significantly higher in ET B (+/−)(92.7±1.2 mmHg)(n= 53, p< 0.05) but not ET A (+/−) KO mice (70.6±1.8 mmHg)(n= 23) when compared to their anaesthetized WT littermates (70.1±0.7 mmHg)(n= 118). A 90 min treatment with either BQ-123 (10 mg/kg), an ET A-selective antagonist, or BQ-928 (10 mg/kg), a mixed ET A/ET B antagonist, administered intraperitoneally, significantly reduced basal MAP of ET B (+/−) KO mice almost to the level of their WT treated counterparts (94.9±4.9 mmHg)(n= 6) vs (+ BQ-123: 59.7±0.3 mmHg, n= 8);(+ BQ-928: 72.4±2.6 mmHg, n= 5). It is worthy of note that BQ-123 significantly reduced basal MAP in WT mice but to a lesser extent than in ET B (+/−) KO mice (69.6±2.3 mmHg, n= 8) vs (+ BQ-123: 57.3±1.4 mmHg, n= 8). In contrast, the ET B-selective antagonist, BQ-788 (10 mg/kg ip), had no significant effect on MAP even after 90 min of treatment (ET B (+/−) KO:(92.3±2.3 mmHg, n= 6) vs (+ BQ-788: 89.7±3.1 mmHg, n= 6); WT:(70.5±3.7 mmHg, n= 7) vs (+ BQ-788: 71.2±2.0 mmHg, n= 6). Therefore heterozygous KO of either ET A-or ET B-receptors significantly alters the phenotypic pressor properties of ET-1. We also suggest that there is less ET clearance in ET B (+/−) KO mice than in WT mice, which can explain the ET A-dependent hypertensive state of the former strain.