# Role of Calcineurin Isoforms in Renal Regulation of Blood Pressure

> **NIH NIH R21** · WRIGHT STATE UNIVERSITY · 2020 · $243,072

## Abstract

PROJECT SUMMARY:
 Approximately 31 million Americans suffer from Chronic Kidney Disease, which is characterized by a
progressive decline in kidney function. One of the major contributing factors to Chronic Kidney Disease is high
blood pressure or hypertension. Despite several classes of anti-hypertensive drugs, blood pressure remains
uncontrolled in more than half of patients. This underscores the need for new drug targets. A feature of
uncontrolled blood pressure is dysregulated renal sodium handling. Sodium handling by the kidney is the
cornerstone of whole body salt and water balance, and subsequent blood pressure homeostasis. Intracellular
mechanisms that regulate renal sodium transporter expression and/or activity offer a new direction for the next
generation of blood pressure therapies.
 By integrating cellular and molecular biology with animal models, our long-term research objective is to
identify and exploit signaling pathways that regulate renal sodium transporters and subsequently sodium
handling and blood pressure. Calcineurin (CnA) is a new player in the regulation of renal sodium handling and
has been identified to be involved in hypertension. Furthermore, clinical and experimental data support a role
for CnA in regulation of renal sodium transporters and blood pressure. Consistent with the literature,
preliminary studies show that CnA inhibition with tacrolimus (general inhibitor) stimulates the upregulation of
the renal sodium chloride cotransporter (NCC). However, understanding of the underlying mechanisms of NCC
regulation, renal sodium handling and blood pressure control are limited by a gap in knowledge regarding the
specific role of each renal CnA isoform (CnAα and CnAβ).
 This R21 grant will delineate the contribution of each CnA isoform to blood pressure regulation. To this
end, we take advantage of innovative transgenic mouse models and cell lines. The outcomes of this R21 grant
will enhance our knowledge of the specific mechanisms by which CnA isoforms regulate blood pressure as
well as inform the development of anti-hypertensive and immunosuppressive therapies.

## Key facts

- **NIH application ID:** 9995480
- **Project number:** 5R21DK119879-04
- **Recipient organization:** WRIGHT STATE UNIVERSITY
- **Principal Investigator:** Clintoria Richards Williams
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $243,072
- **Award type:** 5
- **Project period:** 2018-09-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995480

## Citation

> US National Institutes of Health, RePORTER application 9995480, Role of Calcineurin Isoforms in Renal Regulation of Blood Pressure (5R21DK119879-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9995480. Licensed CC0.

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