TY - JOUR
T1 - Contribution of endogenous endothelin-1 and endothelin-A-receptors to the hypertensive state of endothelin-B heterozygous (+/-) knockout mice
AU - Berthiaume, N.
AU - Yanagisawa, M.
AU - D'Orleans-Juste, P.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2000
Y1 - 2000
N2 - 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 i.p.), 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.
AB - 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 i.p.), 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.
KW - ET(B)-receptors
KW - Hypertension
KW - Knockout
KW - Mouse
KW - Plasmatic clearance
UR - http://www.scopus.com/inward/record.url?scp=0033755604&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033755604&partnerID=8YFLogxK
U2 - 10.1097/00005344-200036001-00062
DO - 10.1097/00005344-200036001-00062
M3 - Article
C2 - 11078340
AN - SCOPUS:0033755604
SN - 0160-2446
VL - 36
SP - S72-S74
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 5 SUPPL. 1
ER -