# Angiotensin (1-12) and Hypertension in the Elderly

> **NIH NIH R21** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $232,500

## Abstract

Project Summary
 The burden of high blood pressure, a major public health problem, is aggravated by an aging human
population. A plethora of experimental data points to angiotensin II (Ang II), as the major contributing factor in
the development of hypertension-related target organ damage. Although data suggested that classic RAS
inhibitors exert positive therapeutic benefits multi-center studies of the long-term effects of these drugs on
cardiovascular morbidity and mortality showed an effectiveness similar to other classes of antihypertensive
drugs. Our hypothesis is that cardiac and renal Ang-(1-12), as a primary precursor for non-renin dependent Ang
II generation, may account for the progressive development of pressure-related target organ damage. The major
goal of this project is to evaluate the therapeutic effects of monoclonal antibodies (mABs) and cell penetrating
nanobodies (Nbs) against the human sequence of Ang-(1-12) through combining high efficacy with improve
treatment adherence. Work in progress characterized mAbs against the C-terminus of human Ang-(1-12).
Whole animal hemodynamic experiments provide proof of concept on the ability of in vivo neutralization of Ang-
(1-12). Research will be performed in a humanized model of hypertension engineered by insertion of the human
angiotensinogen (AGT) gene into the genome of Sprague Dawley rats. Research strategies in male and female
transgenic hypertensive rats will combine continuous blood pressure and heart rate recordings with assessment
of plasma levels of Ang-(1-12), Ang I, Ang II, and Ang-(1-7), measurements of plasma renin activity, and serum
aldosterone, and cardiac and renal function variables. These measures to be taken before and at 1 and 4 weeks
after initiation of therapy with either Ang-(1-12) mAbs or nanobodies (NB). The effectiveness of this
immunotherapy in blood pressure control will be further quantified in experiments in which antibodies are given
to transgenic hypertensive rats in combination with lisinopril or valsartan. The proposed highly innovativestudies
will provide a conceptual basis for novel hypertension treatment strategies involving neutralization of Ang-(1-12).

## Key facts

- **NIH application ID:** 10370035
- **Project number:** 1R21AG070371-01A1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** CARLOS M FERRARIO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $232,500
- **Award type:** 1
- **Project period:** 2021-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370035

## Citation

> US National Institutes of Health, RePORTER application 10370035, Angiotensin (1-12) and Hypertension in the Elderly (1R21AG070371-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10370035. Licensed CC0.

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