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FURIN is a proprotein convertase subtilisin/kexin enzyme important in pro‐renin receptor processing, and FURIN (furin, paired basic amino acid cleaving enzyme) variants are involved in multiple aspects of blood pressure (BP) regulation. Therefore, we examined associations among FURIN variants and the immediate blood pressure (BP) response to bouts of aerobic exercise, termed postexercise hypotension (PEH). Obese (30.9 ± 3.6 kg m−2) Black‐ (n = 14) and White‐ (n = 9) adults 42.0 ± 9.8 year with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) performed three random experiments: bouts of vigorous (VIGOROUS) and moderate (MODERATE) intensity cycling and control. Subjects were then attached to an ambulatory BP monitor for 19 h. We performed deep‐targeted exon sequencing with the Illumina TruSeq Custom Amplicon kit. FURIN genotypes were coded as the number of minor alleles (#MA) and selected for additional statistical analysis based upon Bonferonni or Benjamini–Yekutieli multiple testing corrected P‐values under time‐adjusted linear models for 19 hourly BP measurements. After VIGOROUS over 19 h, as FURIN #MA increased in rs12917264 (P = 2.4E‐04) and rs75493298 (P = 6.4E‐04), systolic BP (SBP) decreased 30.4–33.7 mmHg; and in rs12917264 (P = 1.6E‐03) and rs75493298 (P = 9.7E‐05), diastolic BP (DBP) decreased 17.6–20.3 mmHg among Blacks only. In addition, after MODERATE over 19 h in FURIN rs74037507 (P = 8.0E‐04), as #MA increased, SBP increased 20.8 mmHg among Blacks only. Whereas, after MODERATE over the awake hours in FURIN rs1573644 (P = 6.2E‐04), as #MA increased, DBP decreased 12.5 mmHg among Whites only. FURIN appears to exhibit intensity and race‐dependent associations with PEH that merit further exploration among a larger, ethnically diverse sample of adults with hypertension.

In previous studies, we found an endothelial nitric oxide synthase gene ( NOS3 ) variant rs2070744 associated with the ambulatory blood pressure (BP) response following bouts of moderate and vigorous intensity acute exercise, termed post‐exercise hypotension (PEH). In a validation cohort, we sequenced NOS3 exons for associations with PEH. Obese (30.9 ± 3.6 kg . m −2 ) African American ( n = 14) [AF] and Caucasian ( n = 9) adults 42.0 ± 9.8 years with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) performed three random experiments: bouts of vigorous and moderate intensity cycling and control. Subjects were attached to an ambulatory BP monitor for 19 h. We performed deep‐targeted exon sequencing with the Illumina TruSeq Custom Amplicon kit. Variant genotypes were coded as number of minor alleles (#MA) and selected for additional statistical analysis based upon Bonferonni or Benjamini–Yekutieli multiple testing‐corrected P ‐values under time‐adjusted linear models for 19 hourly BP measurements for each subject. After vigorous intensity over 19 h, among NOS3 variants passing multiple testing thresholds, as the #MA increased in rs891512 ( P = 6.4E‐04), rs867225 ( P = 6.5E‐04), rs743507 ( P = 2.6E‐06), and rs41483644 ( P = 2.4E‐04), systolic (SBP) decreased from 17.5 to 33.7 mmHg; and in rs891512 ( P = 9.7E‐05), rs867225 ( P = 2.6E‐05), rs41483644 ( P = 1.6E‐03), rs3730009 ( P = 2.6E‐04), and rs77325852 ( P = 5.6E‐04), diastolic BP decreased from 11.1 mmHg to 20.3 mmHg among AF only. In contrast, after moderate intensity over 19 h in NOS3 rs3918164, as the #MA increased, SBP increased by 16.6 mmHg ( P = 2.4E‐04) among AF only. NOS3 variants exhibited associations with PEH after vigorous, but not moderate intensity exercise among AF only. NOS3 should be studied further for its effects on PEH in a large, ethnically diverse sample of adults with hypertension to confirm our findings.

We found variants from the Angiotensinogen‐Converting Enzyme ( ACE ), Angiotensin Type 1 Receptor ( AGTR1 ), Aldosterone Synthase ( CYP11B2 ), and Adducin ( ADD1 ) genes exhibited intensity‐dependent associations with the ambulatory blood pressure (BP) response following acute exercise, or postexercise hypotension (PEH). In a validation cohort, we sequenced exons from these genes for their associations with PEH. Obese (30.9 ± 3.6 kg m −2 ) adults ( n = 23; 61% African Americans [AF], 39% Caucasian) 42.0 ± 9.8 years with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) completed three random experiments: bouts of vigorous and moderate intensity cycling and control. Subjects wore an ambulatory BP monitor for 19 h. We performed deep‐targeted exon sequencing using the Illumina TruSeq Custom Amplicon kit. Variant genotypes were coded as number of minor alleles (#MA) and selected for further statistical analysis based upon Bonferonni or Benjamini–Yekutieli multiple testing corrected p‐values under time adjusted linear models for 19 hourly BP measurements per subject. After vigorous intensity over 19 h among ACE , AGTR1 , CYP11B2 , and ADD1 variants passing multiple testing thresholds, as the #MA increased, systolic (SBP) and/or diastolic BP decreased 12 mmHg ( P = 4.5E‐05) to 30 mmHg ( P = 6.4E‐04) among AF only. In contrast, after moderate intensity over 19 h among ACE and CYP11B2 variants passing multiple testing thresholds, as the #MA increased, SBP increased 21 mmHg ( P = 8.0E‐04) to 22 mmHg ( P = 8.2E‐04) among AF only. In this replication study, ACE , AGTR1 , CYP11B2 , and ADD1 variants exhibited associations with PEH after vigorous, but not moderate intensity exercise among AF only. Renal variants should be explored further with a multi‐level “omics” approach for associations with PEH among a large, ethnically diverse sample of adults with hypertension.