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Introduction

Blood pressure is lower on the days we exercise than on the days we do not exercise, a phenomenon referred to as postexercise hypotension.  Postexercise hypotension is the immediate blood pressure lowering effects of a single session of exercise that last for the remainder of the day after exercising.  Postexercise hypotension is gaining increased attention as antihypertensive lifestyle therapy due to its immediate effects.  The heritability of hypertension largely resides in the kidney so that over 10 years ago, we undertook a series of postexercise hypotension studies in which we found genetic variants involved with kidney function exhibited exercise intensity dependent associations with postexercise hypotension.

To duplicate prior findings from our laboratory regarding the influence of genetic predispositions on postexercise hypotension using newer technology, we sequenced the functional sections of genes, termed exons, from a targeted panel of 40 genes for their associations with postexercise hypotension among obese African American and Caucasian adults with hypertension under ambulatory conditions. We found that genetic variants that influence kidney function exhibited associations with postexercise hypotension after vigorous intensity (i.e., significant increases in heart rate, breathing, and sweating and not being able to carry on a conversation), aerobic exercise but not moderate intensity (i.e., noticeable increases in heart rate, breathing, and sweating but still being able to carry on a conversation), aerobic exercise among African Americans only.  Genetic variants that influence kidney function should be explored further for their associations with postexercise hypotension among a large, ethnically diverse sample of adults with hypertension. 

The long term goals of this work are to determine the most effective exercise dose and characterize the types of people exercise works best for as antihypertensive therapy. 

Methods

We used Experiment.com funds to analyze stored blood samples from 23 people that completed our exercise study on postexercise hypotension using the new technology of deep gene sequencing, and the gold standard of blood pressure assessment, ambulatory blood pressure monitoring.

The study participants were 14 middle-aged African American and 9 middle-aged Caucasian men and women in the early stages of hypertension.  The purpose of this project was to confirm findings from our previous work that genetic variants, also termed polymorphisms, that influence kidney function alter the way a person responds to an acute bout of aerobic exercise of different exercise intensities compared to another day on which they do not exercise under ambulatory conditions. 

We constructed a targeted panel of 40 genes from our prior work and a systematic review of the literature, and in collaboration with Jackson Laboratory's Scientific Services (Genome Technologies), we deep sequenced the functional portions of these genes called exons.  The polymorphisms which emerged from these analyses were then examined for their associations with postexercise hypotension. 

 

Results

In this replication cohort using high-throughput exon sequencing, we found that genes involved with kidney function once again exhibited exercise-intensity dependent associations with postexercise hypotension. 

The surprising findings were:  these associations appeared only among the African Americans, only after vigorous intensity exercise, and were of a magnitude that equaled or exceeded that reported with antihypertensive drug treatment.  Indeed, following a bout of vigorous intensity aerobic exercise, blood pressure was decreased 12-30 mmHg after exercise compared to control for 19hr depending upon the kidney genetic variant examined. 

Blood pressure reductions of this magnitude can reduce a person’s high blood pressure into normotensive ranges throughout the remainder of the day when blood pressure is typically at its highest levels.  In contrast, following a bout of moderate intensity aerobic exercise, blood pressure increased 21-22 mmHg among African Americans only.  

 

Our findings are preliminary and are limited by a small sample size, therefore, they should be interpreted with caution.  They illustrate the complexities and challenges of using genomic information to personalize exercise prescriptions to maximize the effectiveness of exercise as antihypertensive therapy.  Yet, they are exciting because they add new and novel information to the exercise genomic literature regarding the immediate antihypertensive effects of exercise.  

Future work should utilize a multi-level "omics" approach involving a focused inquiry of the genome (DNA), transcriptome (RNA), and proteome (proteins) related to kidney function and other important blood pressure regulatory functions among a large, ethnically diverse sample of adults with hypertension to better inform clinical decision making regarding the nuances of the personalized prescription of exercise as antihypertensive lifestyle therapy.