# Exercise Training and Blood Pressure in Hypertension:  Integrated Mechanisms

> **NIH VA I01** · JOHN D DINGELL VA MEDICAL CENTER · 2020 · —

## Abstract

Hypertension is a major public health concern in the U.S. and affects ~70 million adults. Up to 36% of
military Veterans have hypertension which is the primary risk-factor for development of stroke and other cardio-
vascular diseases. Poor nutrition is a risk factor for heart disease and stroke. Fructose intake has increased in
the general population and also in Veterans with up to 25% of Veterans consuming more than 82 g of fructose
per person per day compared with only 0.8 g per person per day in 1970, a 100-fold increase. High fructose
intake exceeds the ability of the liver to convert fructose to glucose, so that fructose enters the bloodstream
which normally does not occur. Fructose ingestion in and of itself has been linked to hypertension by a variety
of mechanisms. Circulating fructose (a) enhances sodium absorption by the gut and decreases renal sodium
excretion, leading to plasma volume expansion, (b) activates the renin-angiotensin system and upregulates
brain angiotensin (Ang II) receptors (AT1R), and (c) can be transported across the blood brain barrier and is
concentrated up to 30-fold in cerebrospinal fluid where it can contribute to sympathetic overdrive. Plasma
volume expansion together with Ang II and sympathetic over activity can then result in increased arterial
pressure. Brain AT1R are upregulated in fructose-fed rats. The subfornical organ (SFO) which is outside the
blood brain barrier is well endowed with AT1R and projects to the paraventricular nucleus (PVN) which
influences sympathetic tone. Fructose has the potential to enhance sympathetic responses by influencing the
neuronal sodium potassium chloride co-transporter (NKCC1) or the potassium chloride co-transporter (KCC2)
within the PVN, similar to actions of fructose on renal transporters. These transporters impart functional
plasticity to GABAergic neurons and limit GABA inhibition of sympathetic outputs, further contributing to
neuroexcitability. Sympathetic input to the kidney stimulates renin secretion and subsequent Ang II generation,
resulting in a vicious cycle. Existing evidence has been indirect with prolonged and/or high exposure to
fructose and cannot distinguish whether fructose ingestion itself results in high Ang II, sympathoexcitation and
hypertension or whether the elevated Ang II and sympathoexcitation are a consequence of the metabolic
syndrome. In this proposal we will test the hypothesis that a high fructose intake combined with a high sodium
chloride diet in rats results in elevated blood pressure due to activation of the renin-angiotensin system and
enhanced RSNA prior to development of the metabolic syndrome that can be mitigated by regular exercise.
Three specific aims will be addressed: (1) fructose-fed, but not glucose-fed, rats on a high NaCl diet will have
higher basal arterial pressure, plasma renin activity (PRA), angiotensin II (Ang II) levels and RSNA within 7 to
28 days as well as greater responses to acute stress; (2) arterial pressure,...

## Key facts

- **NIH application ID:** 10174722
- **Project number:** 5I01RX000851-09
- **Recipient organization:** JOHN D DINGELL VA MEDICAL CENTER
- **Principal Investigator:** Noreen F Rossi
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2012-07-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174722

## Citation

> US National Institutes of Health, RePORTER application 10174722, Exercise Training and Blood Pressure in Hypertension:  Integrated Mechanisms (5I01RX000851-09). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10174722. Licensed CC0.

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