Effects of chlorthalidone treatment on neural-cardiovascular responses to orthostasis in older women with hypertension
Authors: Akins John , Takeda Ryosuke , Washio Takuro , Hissen Sarah , Richey Rauchelle , Romero Steven , Fu Qi 
Published: May 2023

Background: Hypertension remains a significant public health issue for older women (>60 y) in the United States. Diuretics are an important first-line treatment for blood pressure (BP) management. Our group and others have demonstrated that certain diuretics (e.g., chlorthalidone [CTD], hydrochlorothiazide) can increase muscle sympathetic nerve activity (MSNA) and decrease cardiac output (Qc) at rest and during orthostasis. One possible mechanism may be baroreflex-mediated sympathoexcitation due to reduced BP, which may be amplified during orthostasis. Whether this observation holds against untreated, yet BP-matched, hypertension remains unknown. Therefore, we hypothesized that women with hypertension taking CTD would have augmented MSNA and blunted Qc at rest and during graded head-up tilt (HUT) compared to women with untreated hypertension (CON). Methods: Sixteen (8 CTD, 8 CON; 68±4 vs. 70±4 y [mean±SD]) older women with hypertension were studied. All women completed a 24 h ambulatory BP after anti-hypertensive washout alone (CON) or washout followed by 2 wks of CTD treatment (CTD). Systolic and diastolic BP (SBP and DBP), heart rate (HR), MSNA (microneurography), Qc (acetylene rebreathing), and systemic vascular resistance (SVR; mean arterial BP·Qc-1·80) were measured during supine baseline and 5 min each of 30° and 60° HUT. Results: Awake SBP (142±7 vs. 140±2 mmHg; P=0.408) and DBP (82±6 vs. 81±5 mmHg; P=0.866) were not different between CTD and CON, nor were resting cuff SBP, cuff DBP, and HR (all P>0.05). No differences were noted between CTD and CON for resting MSNA burst frequency (32±11 vs. 24±12 bursts·min-1; P=0.160) or incidence (49±17 vs. 38±17 bursts·100 heartbeats-1; P=0.197). Further, there were no differences between CTD and CON for Qc (4.8±0.9 vs. 5.1±0.9 L·min-1; P=0.529) or SVR (1649±361 vs. 1562±336 dyne·s·cm-5; P=0.637). While DBP and HR increased across HUT (both P<0.05), there were no group differences for ΔSBP, ΔDBP, or ΔHR (all P>0.05). While ΔMSNA burst frequency/incidence and ΔSVR were not different between groups during HUT (all P>0.05), there was a trend for ΔQc to be lower in the CTD group ( P=0.067). Conclusions: Contrary to our hypothesis, MSNA appeared to not be augmented in CTD at rest or during graded HUT relative to CON. Additionally, though resting Qc was not reduced, there was a trend towards a lower Qc during tilt in the CTD group. Accordingly, these preliminary data suggest that CTD may not elicit sympathetic hyperactivity relative to untreated, BP-matched hypertension, but may still attenuate Qc during orthostasis in older women with hypertension. Supported by the National Institutes of Health (R01AG059314) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.