An activated renin–angiotensin system maintains normal blood pressure in aryl hydrocarbon receptor heterozygous mice but not in null mice
It has been postulated that fetal vascular abnormalities in aryl hydrocarbon receptor null ( ahr −/−) mice may alter cardiovascular homeostasis in adulthood. We tested the hypothesis that blood pressure regulation in adult heterozygous mice ( ahr +/−) would be normal, compared to ahr −/− mice, since...
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Published in | Biochemical pharmacology Vol. 80; no. 2; pp. 197 - 204 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Amsterdam
Elsevier Inc
15.07.2010
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | It has been postulated that fetal vascular abnormalities in aryl hydrocarbon receptor null (
ahr
−/−) mice may alter cardiovascular homeostasis in adulthood. We tested the hypothesis that blood pressure regulation in adult heterozygous mice (
ahr
+/−) would be normal, compared to
ahr
−/− mice, since no vascular abnormalities have been reported in the heterozygote animals. Mean arterial blood pressure (MAP) was measured using radiotelemetry prior to and during treatment with inhibitors of the autonomic nervous system, nitric oxide synthase (NOS), angiotensin converting enzyme (ACE), or endothelin-1 A receptor (ET
A). Also, indices of renin–angiotensin system (RAS) activation were measured.
ahr
+/− and
ahr
−/− mice were normotensive and hypotensive, respectively, compared to wild-type (
ahr
+/+) littermates. Responses of all genotypes to autonomic nervous system inhibition were normal.
ahr
+/− mice responded normally to NOS inhibition, while the responses of
ahr
−/− mice were significantly blunted. In contrast,
ahr
+/− mice were significantly more responsive to inhibition of ACE, an ET
A antagonist, or both, while
ahr
−/− mice were significantly less responsive to ACE inhibition and more responsive to an ET
A antagonist.
ahr
+/− mice also exhibited significant increases in plasma renin and ACE activity, plasma sodium, and urine osmolality, indicative of RAS activation. Thus, normotension in
ahr
+/− mice appears to be maintained by increased RAS and ET-1 signaling, while hypotension in
ahr
−/− mice may result from decreased RAS signaling. In conclusion, despite the lack of overt fetal vascular abnormalities in
ahr
+/− mice, the loss of a single
ahr allele has a significant effect on blood pressure regulation. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present Address: Department of Internal Medicine, University of Michigan, Ann Arbor, MI |
ISSN: | 0006-2952 1873-2968 |
DOI: | 10.1016/j.bcp.2010.03.023 |