In:
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 276, No. 4 ( 1999-04-01), p. R1071-R1077
Abstract:
Exogenously administered endothelin (ET) elicits both pressor and depressor responses through the ET A and/or the ET B receptor on vascular smooth muscle cells and ET B on endothelial cells. To test whether ET B has pressor or depressor effects under basal physiological conditions, we determined arterial blood pressure (BP) in ET B -deficient mice obtained by crossing inbred mice heterozygous for targeted disruption of the ET B gene with mice homozygous for the piebald ( s) mutation of the ET B gene ( ET B s/s ). F 1 ET B −/s and ET B +/s progeny share an identical genetic background but have ET B levels that are ∼[Formula: see text]and [Formula: see text] , respectively, of wild-type mice ( ET B +/+ ). BP in ET B −/s mice was significantly higher, by ∼20 mmHg, than that in ET B +/s or ET B +/+ mice. Immunoreactive ET-1 concentration in plasma as well as respiratory parameters was not different between ET B −/s and ET B +/s mice. A selective ET B antagonist, BQ-788, increased BP in ET B +/s and ET B +/+ but not in ET B −/s mice. Pretreatment with indomethacin, but not with N G -monomethyl-l-arginine, can attenuate the observed pressor response to BQ-788. The selective ET A antagonist BQ-123 did not ameliorate the increased BP in ET B −/s mice. Moreover, BP in mice heterozygous for targeted disruption of the ET A gene was not different from that in wild-type controls. These results suggest that endogenous ET elicits a depressor effect through ET B under basal conditions, in part through tonic production of prostaglandins, and not through secondary mechanisms involving respiratory control or clearance of circulating ET.
Type of Medium:
Online Resource
ISSN:
0363-6119
,
1522-1490
DOI:
10.1152/ajpregu.1999.276.4.R1071
Language:
English
Publisher:
American Physiological Society
Publication Date:
1999
detail.hit.zdb_id:
1477297-8
SSG:
12
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