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Angiotensin II type 2 receptor inhibits cell proliferation and activates tyrosine phosphatase
S Tsuzuki1, T Matoba, S Eguchi
1Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
Abstract:
The angiotensin II type 2 (AT2) receptor inhibits basic fibroblast growth factor-induced proliferation of R3T3 fibroblast cells and transiently stimulates a vanadate-sensitive phosphotyrosine phosphatase, strongly suggesting that AT2 is a mitogen inhibitor. We generated AT2 gene-null mice that showed increased blood pressure, indicating the hypotensive action of AT2. However, inhibition of renomedullary AT2 by selective antagonists, as reported by Sassard and associates, show that AT2 suppresses pressure natriuresis. Thus, both AT1 and AT2 work in the direction of sodium retention, suggesting a unique role for angiotensin II in the kidney in terms of blood pressure regulation and sodium metabolism.
Insights
The angiotensin II type 2 (AT2) receptor acts as a mitogen inhibitor. AT2 gene-null mice exhibited higher blood pressure, suggesting AT2
Area of Science:
- Cardiovascular physiology
- Renal physiology
- Cell signaling
Background:
- The angiotensin II type 2 (AT2) receptor's role in blood pressure regulation and sodium metabolism is complex and not fully understood.
- Previous studies suggest AT2 may act as a mitogen inhibitor and influence vascular tone.
Purpose of the Study:
- To investigate the role of the AT2 receptor in blood pressure regulation and sodium balance using gene-null mice.
- To elucidate the signaling pathways modulated by AT2, specifically its effect on phosphotyrosine phosphatase activity.
Main Methods:
- Generation and characterization of AT2 gene-null mice.
- Measurement of blood pressure in wild-type and AT2-deficient mice.
- Assessment of vanadate-sensitive phosphotyrosine phosphatase activity in response to AT2 stimulation.
- Analysis of pressure natriuresis in the presence of selective AT2 antagonists.
Main Results:
- AT2 gene-null mice displayed elevated blood pressure compared to wild-type controls.
- The AT2 receptor was shown to inhibit basic fibroblast growth factor-induced R3T3 fibroblast cell proliferation.
- AT2 stimulation transiently activated a vanadate-sensitive phosphotyrosine phosphatase.
- Inhibition of renomedullary AT2 by antagonists suppressed pressure natriuresis, indicating a role in sodium retention.
Conclusions:
- The AT2 receptor functions as a mitogen inhibitor.
- Both AT1 and AT2 receptors contribute to sodium retention, highlighting a unique dual role for angiotensin II in renal sodium handling and blood pressure homeostasis.
- These findings suggest a novel mechanism for blood pressure regulation involving the AT2 receptor in the kidney.