An activated renin-angiotensin system maintains normal blood pressure in aryl hydrocarbon receptor heterozygous mice but not in null mice

Nan Zhang, Larry N. Agbor, Jason A. Scott, Tyler Zalobowski, Khalid M. Elased, Alicia Trujillo, Melissa Skelton Duke, Valerie Wolf, Mary T. Walsh, Jerry L. Born, Linda A. Felton, Jian Wang, Wei Wang, Nancy L. Kanagy, Mary K. Walker

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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 (ETA). 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 ETA antagonist, or both, while ahr-/- mice were significantly less responsive to ACE inhibition and more responsive to an ETA 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.

Original languageEnglish (US)
Pages (from-to)197-204
Number of pages8
JournalBiochemical Pharmacology
Issue number2
StatePublished - Jul 2010
Externally publishedYes


  • Angiotensin II
  • Aryl hydrocarbon receptor
  • Blood pressure
  • Heterozygote
  • Vasocontraction

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology


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