Unknown

Dataset Information

0

Mitogen-activated protein kinases mediate upregulation of hypothalamic angiotensin II type 1 receptors in heart failure rats.


ABSTRACT: In heart failure (HF), angiotensin II type 1 receptor (AT(1)-R) expression is upregulated in brain regions regulating sympathetic drive, blood pressure, and body fluid homeostasis. However, the mechanism by which brain AT(1)-R are upregulated in HF remains unknown. The present study examined the hypothesis that the angiotensin II (Ang II)-triggered mitogen-activated protein kinases (MAPKs) p44/42, p38, and c-Jun N-terminal kinase contribute to upregulation of the AT(1)-R in the hypothalamus of rats with HF. AT(1)-R protein, AT(1)-R mRNA, and AT(1)-R immunoreactivity increased in the paraventricular nucleus of hypothalamus and the subfornical organ of rats with ischemia-induced HF compared with sham-operated controls. Phosphorylated p44/42 MAPK, c-Jun N-terminal kinase, and p38 MAPK also increased in paraventricular nucleus and subfornical organ. A 4-week ICV infusion of the AT(1)-R antagonist losartan decreased AT(1)-R protein and phosphorylation of p44/42 MAPK, c-Jun N-terminal kinase, and p38 MAPK in the HF rats. A 4-week ICV infusion of the p44/42 MAPK inhibitor PD98059 or the c-Jun N-terminal kinase inhibitor SP600125 significantly decreased AT(1)-R protein and AT(1)-R immunoreactivity in the paraventricular nucleus and subfornical organ, but the p38 MAPK inhibitor SB203580 did not. Treatment with ICV losartan, PD98059, and SP600125 had no effect on AT(1)-R expression by Western blot in sham-operated rats. In untreated HF rats 4 weeks after coronary ligation, a 3-hour ICV infusion of PD98059, SP600125, or losartan reduced AT(1)-R mRNA in paraventricular nucleus and subfornical organ. These data indicate that MAPK plays an important role in the upregulation of AT(1)-R in the rat forebrain in HF and suggest that Ang II upregulates its own receptor by this mechanism.

SUBMITTER: Wei SG 

PROVIDER: S-EPMC2790407 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

Mitogen-activated protein kinases mediate upregulation of hypothalamic angiotensin II type 1 receptors in heart failure rats.

Wei Shun-Guang SG   Yu Yang Y   Zhang Zhi-Hua ZH   Weiss Robert M RM   Felder Robert B RB  

Hypertension (Dallas, Tex. : 1979) 20080902 4


In heart failure (HF), angiotensin II type 1 receptor (AT(1)-R) expression is upregulated in brain regions regulating sympathetic drive, blood pressure, and body fluid homeostasis. However, the mechanism by which brain AT(1)-R are upregulated in HF remains unknown. The present study examined the hypothesis that the angiotensin II (Ang II)-triggered mitogen-activated protein kinases (MAPKs) p44/42, p38, and c-Jun N-terminal kinase contribute to upregulation of the AT(1)-R in the hypothalamus of r  ...[more]

Similar Datasets

| S-EPMC8395442 | biostudies-literature
| S-EPMC2785116 | biostudies-literature
| S-EPMC3911290 | biostudies-literature
| S-EPMC9530026 | biostudies-literature
| S-EPMC4765092 | biostudies-literature
| S-EPMC3655907 | biostudies-literature
| S-EPMC1218581 | biostudies-other
| S-EPMC1373668 | biostudies-literature
| S-EPMC1560367 | biostudies-literature
| S-EPMC10643657 | biostudies-literature