The Effect of Physical Activity on Hemodynamic Response to Angiotensin Converting Enzyme Inhibition in Hypertension

Abstract

PURPOSE: Physical activity (PA) can reduce blood pressure (BP) in hypertensive populations. Although underlying mechanisms remain unclear, an interaction with the renin-angiotensin-aldosterone system (RAAS) is a logical focus of exploration. We conducted a nested cohort analysis to determine if reported level of PA was associated with vascular responsiveness to acute angiotensin converting enzyme inhibition (ACEi). METHODS: Data were extracted from the HyperPATH dataset, which is an ongoing program to identify genetic mechanisms underlying cardiometabolic risk. Individuals with hypertension who completed a physical activity self-assessment and who had completed hormonal assessment (serum aldosterone [ALDO] and plasma renin activity [PRA]) and vascular response (BP) to a single dose of an ACEi (captopril 25mg) were included for analysis. All participants (n=144) were studied in a clinical research center after overnight, supine, fasting status and on a sodium, potassium, and calcium controlled diet for 7 days. PA was reported as 1) no additional PA, 2) little, 3) moderate, or 4) high amounts of exercise. The response to ACEi was evaluated by ANOVA or multivariate regression when appropriate, with all analyses adjusted for age, sex, race, and BMI. RESULTS: As expected, both acute ACEi and increased PA levels were significantly associated with reduced systolic BP (p<0.05). However, individuals who reported high amounts of exercise displayed a greater BP lowering effect from ACEi compared to those who reported moderate (-14.8 ± 8.1 mmHg vs -8.4 ± 9.9 mmHg, p<0.01) or no additional PA (-14.8 ± 8.1mmHg vs -2.6 ± 9.9 mmHg, p<0.001). Exploratory analyses indicated high amounts of PA were associated with: a reduced heart rate when compared to no PA (54.2±7.7 bpm vs 66.4±9.8 bpm, p<0.001), reductions in PRA (0.42±0.48 ng/ml/hr vs 0.59±0.52 ng/ml/hr, p<0.05), and reductions in ALDO (β=-0.44, CI=0.19-0.70, p=0.001). CONCLUSIONS: Higher levels of self-reported PA are associated with decreased BP, and acute ACEi resulted in an augmented BP lowering effect in hypertensive subjects. PA is inversely correlated with RAAS activity. These data shed light on how physical activity interacts with vascular function in RAAS activity and suggest that PA and ACEi medications may act synergistically.