# ROLE OF SYMPATHETIC FUNCTION IN GERIATRIC HYPERTENSION

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1992 · $88,217

## Abstract

The overall objective of this proposal is to determine the extent to which
age-related changes in sympathetic nervous system (SNS) function,
sensitivity to the metabolic effects of insulin, and salt-sensitivity of
blood pressure contribute to hypertension in the elderly.  Three hypotheses
will be tested.  Data from our initial studies suggest that there is an
age-related increase in SNS activity and a decrease in responsiveness to
alpha-adrenergic stimulation in normotensive elderly which appears to
represent appropriate down-regulation to their heightened level of SNS
activity.  Hypothesis 1: Hypertension in elderly humans is related in part
to an age-related increase in SNS activity coupled with diminished ability
to normally down-regulate alpha-adrenergic responsiveness.  Four specific
aims pertain to this hypothesis: 1) To determine if an age-related increase
in systemic SNS activity (the rate of norepinephrine (NE) release into an
extravascular compartment derived from NE kinetics) occurs in hypertensive
as well as normotensive elderly humans, 2) To develop a flow-compartment
model for regional norepinephrine kinetics to determine the level of SNS
activity in the forearm, 3) To determine if the responsiveness to
alpha-adrenergic stimulation measured in platelet membrane
alpha2-adrenergic receptors and by vascular responses to alpha-adrenergic
stimulation (alpha-adrenergic agonist mediated changes in forearm blood
flow and venoconstriction) is increased in elderly hypertensives relative
to normotensives, and 4) To determine if there is altered regulation of
alpha-adrenergic responsiveness mediated by changes in SNS activity in
elderly hypertensives.

Older hypertensives are more likely to have insulin resistance and
salt-sensitivity of blood pressure.  The potential interactions between
insulin and sodium and SNS activity will be tested in Hypothesis 2:
Salt-sensitivity of blood pressure will be greatest in the setting of
decreased sensitivity to the metabolic effects of insulin and heightened
SNS activity, and Hypothesis 3: During dietary salt loading,
sodium-sensitive hypertensive elderly will demonstrate increased SNS
activation compared with sodium-resistant hypertensive and sodium-resistant
normotensive elderly controls.  Sensitivity to the metabolic effects of
insulin will be determined by analysis of glucose and insulin values
obtained during a tolbutamide-assisted intravenous glucose tolerance test.
Salt sensitivity of blood pressure will be determined from the difference
in blood pressure between a low-salt compared to a high-salt diet.

We hypothesize that the compensatory mechanisms which normally allow
adaptation to these ow related changes (e.g. down-regulation of
alpha-adrenergic responsiveness or response to dietary sodium) are impaired
in older hypertensives.  The outcome of these studies will be new insights
into the interactions between aging, SNS function, insulin resistance and
salt-sensitivity of blood pressure in older h...

## Key facts

- **NIH application ID:** 3122021
- **Project number:** 1R01AG010053-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **SAM.gov UEI:** GNJ7BBP73WE9
- **Principal Investigator:** Mark A Supiano
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $88,217
- **Award type:** 1
- **Project period:** 1992-09-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122021

## Citation

> US National Institutes of Health, RePORTER application 3122021, ROLE OF SYMPATHETIC FUNCTION IN GERIATRIC HYPERTENSION (1R01AG010053-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122021. Licensed CC0.

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