The Role of Endothelin‐1 in Exercising Blood Flow and Blood Pressure Regulation in Patients with Hypertension
Authors: Craig Jesse C , Broxterman Ryan M , La Salle D Taylor , Cerbie James , Ratchford Stephen M , Gifford Jayson R , Bunsawat Kanokwan , Nelson Ashley D , Bledsoe Amber D , Morgan David E , Wray D Walter , Richardson Russell S , Trinity Joel D 
Published: June 2021

BackgroundPatients with hypertension (HTN) exhibit impaired muscle blood flow and an exaggerated increase in arterial blood pressure during exercise, which may limit exercise capacity and increase the risk of adverse cardiovascular events during or after exercise. We have previously identified that endothelin (ET)‐1 critically regulates both muscle blood flow and blood pressure during exercise in young and older healthy individuals. However, the contribution of this pathway to the cardiovascular responses during exercise in HTN is not known. Therefore, this investigation sought to examine the impact of ETA receptor antagonism via intra‐arterial BQ‐123 administration on leg blood flow (LBF) and arterial blood pressure during exercise in HTN. Specifically, we tested the hypotheses that BQ‐123 infusion would: 1) increase LBF and 2) attenuate the increase in arterial blood pressure during single‐leg knee extension exercise in HTN.MethodsEight volunteers with HTN (2 women, 6 men; 46 ± 4 years; resting blood pressure 136 ± 3/86 ± 6 mmHg) completed the protocol following a 2 week withdrawal of antihypertensive medications. The common femoral artery and femoral vein were catheterized for drug infusion, blood collection, and measurements of intravascular pressures. LBF was measured by Doppler ultrasound. Following a period of rest, during which resting hemodynamics were assessed, subjects exercised for 3 min at absolute (0, 5, 10, 15 W) and relative (40, 60, 80% peak power) intensities with continued saline infusion. Following 90 min of recovery, BQ‐123 was infused for 45 min and the exercise bouts were repeated.ResultsBQ‐123 increased LBF at rest (79 ± 31 ml/min) and evoked a progressive increase in LBF during exercise (range: 292 ± 72 ml/min at 5 W to 994 ± 230 ml/min at 80% of peak power; all p < 0.05). BQ‐123 reduced MAP at rest (−7 ± 1 mmHg; p < 0.001) and the lower work rates (i.e. 0, 5, 10 W; all p < 0.05), but not the higher intensities (i.e. 15 W, 40, 60%; all p > 0.05) including 80% (BQ‐123: 142 ± 7 vs Saline: 143 ± 7 mmHg, p = 0.34).ConclusionsThe present findings indicate that ET‐1 contributes to the regulation of blood flow and blood pressure at rest and during exercise in HTN. Interestingly, while the increase in blood flow following ET‐1 antagonism occurred at all exercise intensities and progressed with increasing intensity, the reduction in blood pressure was only evident at rest and lower intensities. Therapeutically, targeting the ET‐1 system may be a viable option to improve muscle blood flow in hypertensive patients during exercise.Support or Funding InformationThis study was supported by NIH NRSA 2T32HL007576‐31 (J. C. Craig); VA RR&D Grant IK2RX001215 (J. D. Trinity) and Merit Awards E1697R and E6910R (R. S. Richardson); AHA 14SDG1850039 (J. D. Trinity).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.