# CAPTOPRIL AND ANGIOTENSIN VASCULAR EFFECTS IN SENESCENCE

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 1992 · $131,936

## Abstract

Impaired homeostatic control of the circulatory system contributes to the
high incidence of morbid and fatal cardiovascular episodes afflicting the
elderly. Chronobiologic changes in the renin-angiotensin system (RAS),
therefore, may represent important pathophysiologic modifications during
the aging process. A number of studies have documented age-associated
reductions in plasma renin activity (PRA) and plasma aldosterone
concentration. Based on these data, many investigators have considered RAS
activity to diminish during aging and predicted that angiotensin converting
enzyme (ACE) inhibitors would not be efficacious in treating hypertension
in the geriatric population. The conclusions regarding RAS activity,
however, are inferences as few studies in elderly humans have measured
angiotensin II (All), biologically the most important component of the RAS.
Perhaps due to limitations in the assays employed to measure All,
discordant and paradoxical results have been noted regarding the
relationship between PRA and All concentration. Furthermore, All's vascular
effect for a particular level of PRA has not been well characterized. Thus,
it has not been shown that PRA remains a reliable index of RAS activity in
senescence. Importantly, the accrued results from several lines of
investigation, including data demonstrating a continued efficacy of ACE
inhibitors in the elderly, suggest that the RAS continues to play an
important role in the homeostatic control of blood pressure throughout all
of life. This proposal will explore this issue in elderly humans by
elucidating captopril's mechanism of action and characterizing the vascular
activity of the RAS. Captopril's kinetic-dynamic relationship will be
determined employing sensitive and specific assays for the drug and various
response parameters. In addition to this manipulation of the RAS, other
physiologic and pharmacologic maneuvers designed to alter the system will
be used in order to study the relationships between PRA, All concentration
and vascular reactivity. PRA will be measured by conventional methods and
the true All concentration will be determined after chromatographic
separation from interfering metabolites. To evaluate the vascular effect
of All that corresponds to a particular state of RAS activity, the
localized vascular response to All infused into the brachial artery will
be measured by venous occlusion plethysmography. For comparison, young
control subjects will also be studied. Results from this proposal should
provide further insights into the functional significance of the
age-associated affects on the RAS which, in turn, may influence treatment
strategies for diseases such as hypertension in the elderly.

## Key facts

- **NIH application ID:** 3121435
- **Project number:** 5R01AG009560-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **SAM.gov UEI:** SHHBRBAPSM35
- **Principal Investigator:** JAMES VOELKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $131,936
- **Award type:** 5
- **Project period:** 1991-02-01 → 1994-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121435

## Citation

> US National Institutes of Health, RePORTER application 3121435, CAPTOPRIL AND ANGIOTENSIN VASCULAR EFFECTS IN SENESCENCE (5R01AG009560-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121435. Licensed CC0.

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