Paton, Julian F. R.

Introduction Baroreflex activation through electrical carotid sinus stimulation has been developed for the treatment of patients with arterial hypertension not sufficiently responding to pharmacological therapy. Previous studies suggested that peripheral chemoreflex afferents located in proximity to carotid baroreceptors are tonically active in hypertensive patients and may inhibit baroreflex responses. Therefore, we hypothesized that peripheral chemoreflex activation attenuates the efficacy of electrical carotid sinus stimulation. Methods We screened 35 patients with an implanted electrical carotid sinus stimulator. Of those, 11 patients exhibited a consistent acute depressor response and were included in the study (7 men/4 women, age: 67±8 years, BMI: 31.6±5.2 kg/m 2 , 6±2 antihypertensive drug classes). We assessed responses to electrical baroreflex stimulation during normoxia, isocapnic hypoxia (SpO2: 79.0±1.5%), and hyperoxia (40% end‐tidal O2 fraction) by recording ECG, blood pressure (SBP), ventilation, SpO2, end‐tidal CO2 and O2 fractions, and muscle sympathetic nerve activity (MSNA). Results During normoxia, baroreflex activation reduced SBP from 164±27 to 151±25 mmHg (means±SD, p<0.001), HR from 64±13 to 61±13 bpm (p=0.002), and MSNA from 42±12 to 36±12 bursts/min (p=0.004). Hypoxia increased SBP 8±12 mmHg (p=0.057), HR 10±6 bpm (p<0.001), MSNA 7±7 bursts/min (p=0.031), and ventilation 10±7 l/min (p=0. 002). However, responses to electrical carotid sinus stimulation did not differ between hypoxic and hyperoxic conditions; SBP: −15±7 vs −14±8 mmHg (p=0.938), HR: −2±3 vs −2±2 bpm (p=0.701), and MSNA: −6±4 vs −4±3 bursts/min (p=0.531). Conclusion The main finding of our study is that moderate peripheral chemoreflex activation does not attenuate acute responses to electrical baroreflex activation therapy (BAT) in patients with resistant hypertension. These patients provide insight in human baroreflex physiology and baroreflex‐chemoreflex interactions that could not be gained otherwise. Support or Funding Information Financial support by Boston Scientific Corporation (St. Paul, MN, U.S.A.) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Arterial baroreflex activation through electrical carotid sinus stimulation has been developed for the treatment of resistant hypertension. Previous studies suggested that the peripheral chemoreflex is tonically active in hypertensive patients and may inhibit baroreflex responses. We hypothesized that peripheral chemoreflex activation attenuates baroreflex efficacy evoked by electrical carotid sinus stimulation. We screened 35 patients with an implanted electrical carotid sinus stimulator. Of those, 11 patients with consistent acute depressor response were selected (7 men/4 women, age: 67±8 years, body mass index: 31.6±5.2 kg/m 2 , 6±2 antihypertensive drug classes). We assessed responses to electrical baroreflex stimulation during normoxia, isocapnic hypoxia (SpO 2 : 79.0±1.5%), and hyperoxia (40% end-tidal O 2 fraction) by measuring heart rate, blood pressure, ventilation, oxygen saturation, end-tidal CO 2 and O 2 fractions, and muscle sympathetic nerve activity. During normoxia, baroreflex activation reduced systolic blood pressure from 164±27 to 151±25 mm Hg (mean±SD, P <0.001), heart rate from 64±13 to 61±13 bpm ( P =0.002), and muscle sympathetic nerve activity from 42±12 to 36±12 bursts/min ( P =0.004). Hypoxia increased systolic blood pressure 8±12 mm Hg ( P =0.057), heart rate 10±6 bpm ( P <0.001), muscle sympathetic nerve activity 7±7 bursts/min ( P =0.031), and ventilation 10±7 L/min ( P =0.002). However, responses to electrical carotid sinus stimulation did not differ between hypoxic and hyperoxic conditions: systolic blood pressure: −15±7 versus −14±8 mm Hg ( P =0.938), heart rate: −2±3 versus −2±2 bpm ( P =0.701), and muscle sympathetic nerve activity: −6±4 versus −4±3 bursts/min ( P =0.531). We conclude that moderate peripheral chemoreflex activation does not attenuate acute responses to electrical baroreflex activation therapy in patients with resistant hypertension. These patients provided insight into human baroreflex-chemoreflex interactions that could not be gained otherwise.

Key points We have developed a simple analytical method for quantifying the transduction of sympathetic activity into vascular tone. This method demonstrates that as women age, the transfer of sympathetic nerve activity into vascular tone is increased, so that for a given level of sympathetic activity there is more vasoconstriction. In men, this measure decreases with age. Test–re‐test analysis demonstrated that the new method is a reliable estimate of sympathetic transduction. We conclude that increased sympathetic vascular coupling contributes to the age‐related increase in blood pressure that occurs in women only. This measure is a reliable estimate of sympathetic transduction in populations with high sympathetic nerve activity. Thus, it will provide information regarding whether treatment targeting the sympathetic nervous system, which interrupts the transfer of sympathetic nerve activity into vascular tone, will be effective in reducing blood pressure in hypertensive patients. This may provide insight into which populations will respond to certain types of anti‐hypertensive medication. Abstract Sex and age differences in the sympathetic control of resting blood pressure (BP) may be due to differences in the transduction of sympathetic nerve activity (SNA) into vascular tone. Current methods for dynamically quantifying transduction focus on the relationship between SNA and vasoconstriction during a pressor stimulus, which increases BP and may be contra‐indicated in patients. We describe a simple analytical method for quantifying transduction under resting conditions. We performed linear regression analysis of binned muscle SNA burst areas against diastolic BP (DBP). We assessed whether the slope of this relationship reflects the transduction of SNA into DBP. To evaluate this, we investigated whether this measure captures differences in transduction in different populations. Specifically, we (1) quantified transduction in young men (YM), young women (YW), older men (OM) and postmenopausal women (PMW); and (2) measured changes in transduction during β‐blockade using propranolol in YW, YM and PMW. YM had a greater transduction vs . OM (0.10 ± 0.01 mmHg (% s) −1 , n = 23 vs . 0.06 ± 0.01 mmHg (% s) −1 , n = 18; P = 0.003). Transduction was lowest in YW (0.02 ± 0.01 mmHg (% s) −1 , n = 23) and increased during β‐blockade (0.11 ± 0.01 mmHg (% s) −1 ; P < 0.001). Transduction in PMW (0.07 ± 0.01 mmHg (% s) −1 , n = 23) was greater compared to YW ( P = 0.001), and was not altered during β‐blockade (0.06 ± 0.01 mmHg (% s) −1 ; P = 0.98). Importantly, transduction increased in women with age, but decreased in men. Transduction in women intersected that in men at 55 ± 1.5 years. This measure of transduction captures age‐ and sex‐differences in the sympathetic regulation of DBP and may be valuable in quantifying transduction in disease. In particular, this measure may help target treatment strategies in specific hypertensive subpopulations.