# Renal Pericytes as a Target for Angiotensin II Signaling in Hypertension

> **NIH NIH K01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $127,537

## Abstract

PROJECT SUMMARY
The renin-angiotensin-system (RAS) plays a central role in regulating systemic blood pressure. This is illustrated
by the proven benefit of RAS-targeted drugs such as angiotensin receptor blockers, which are critical to the
treatment of hypertension, heart failure and kidney disease. The actions of the RAS depend on the peptide
angiotensin II (ang II) acting on cells that express the G-protein coupled type 1 angiotensin receptor (human:
AT1; mouse: AT1a). Our group has been at the forefront of unmasking cell-specific roles of ang II signaling
within different cell populations in the kidney. These studies have revealed novel roles for ang II to act distinctly
in different cell types to drive pathogenic mechanisms associated with hypertension. This suggests that the
overall, systemic effect of ang II on blood pressure results from the cumulative actions of ang II on multiple cell
types within the body. Our preliminary studies analyzed recently published single-cell RNA Sequencing datasets
to explore the cell-specific expression of angiotensin receptors within the kidney. We find that pericytes, a mural
cell type associated with capillaries and the glomerulus, express the mouse AT1a receptor. Additionally, we
confirmed this by measuring AT1a expression from rapidly sorted pericytes from the kidney. However, the role
of angiotensin signaling in pericytes remains under-examined. This is despite multiple lines of evidence that
suggest renal pericytes play a central role in regulating blood pressure and renal injury, angiotensin-linked
processes which are pathologically altered in hypertension and chronic kidney disease. This project will test the
overall hypothesis that angiotensin II signaling within pericytes contributes to the development of hypertension
and renal injury. This candidate has developed a novel mouse line which has inducible pericyte-specific deletion
of the AT1a receptor. First, the contribution of pericyte ang II signaling to blood pressure control will be
determined under baseline conditions and during ang II hypertension. Next, the effect of ang II signaling within
pericytes on renal injury in the context of hypertension will be assessed. This research will be carried out by an
applicant with excellent training in biomedical research with a strong publication record. The training for this
proposal will occur at Oregon Health & Science University within the Division of Nephrology and Hypertension
under the primary mentorship of Dr. Susan Gurley a leader in the field of cell-specific actions of RAS signaling
in the kidney. This project will also be supported by two other co-mentors: Dr. Anusha Mishra, an expert on
pericyte biology and microvascular blood flow, and Dr. Lynne Sakai, an expert on vascular fibrotic signaling.
Career development activities include training in mouse micro-surgery, ex vivo slice imaging, assessment of
renal pathology, and bioinformatic analysis of single-cell RNA sequencing datasets. This tr...

## Key facts

- **NIH application ID:** 10431802
- **Project number:** 5K01DK121737-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Jonathan W Nelson
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $127,537
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10431802

## Citation

> US National Institutes of Health, RePORTER application 10431802, Renal Pericytes as a Target for Angiotensin II Signaling in Hypertension (5K01DK121737-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10431802. Licensed CC0.

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