Antihypertensive Mechanism of Orally Administered Acetylcholine in Spontaneously Hypertensive Rats

Figures

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  Figure 1. Long-term antihypertensive effects of repeated oral administration of acetylcholine (ACh; dose: 10−8 mol/kg body weight) or pure water as a control in spontaneously hypertensive rats. Changes in (a) systolic blood pressure (SBP), (b) diastolic blood pressure (DBP), and (c) count of renal sympathetic nervous activity (RSNA) spikes measured directly using a telemetry method. Changes in excretion of (d) urinary catecholamines. The data in (a–d) were calculated as the change in the values from before administration. Plasma (e) angiotensin II (Ang II) concentration on day 30. Each data point and error bar represents mean ± standard error. Data from the long-term study were analyzed by two-tailed Welch’s t-test. * p < 0.05, ** p < 0.01. AD: adrenaline; NAD: noradrenaline.

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  Figure 2. Acute antihypertensive effects of single oral administration of acetylcholine (ACh; dose: 10−8 mol/kg body weight) or pure water as a control in spontaneously hypertensive rats. Changes in (a) systolic blood pressure (SBP), (b) diastolic blood pressure (DBP), and (c) lumbar sympathetic nervous activity (LSNA) in SHRs in which LSNA was measured using a telemetry method (control [n = 6], ACh [n = 6]). Changes in (d) SBP, (e) DBP, and (f) renal sympathetic nervous activity (RSNA) in SHRs in which RSNA was measured using the telemetry method (control [n = 6], ACh [n = 6]). The data in (a–f) were calculated as change in values from before administration. The time course charts show mean values every 1 s until 12 h after administration and then averaged for each group. The box plots were drawn from values individually averaged every 3 h until 12 h after administration. The data from 15 min after administration were not used in the analysis to exclude the effect of the drinking action. Urinary excretions of (g) adrenaline (AD) and noradrenaline (NAD) (control [n = 6], ACh [n = 6]) are shown; data point and error bar represent the mean ± standard error. The data of telemetry measurement…

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  Figure 3. Changes in (a) systolic blood pressure (SBP) and (b) diastolic blood pressure (DBP) after oral administration of 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, 10−8 mol/kg body weight [BW]), which is an M3 muscarinic acetylcholine receptor (M3 mAChR) antagonist, acetylcholine (ACh, 10−8 mol/kg BW), and both substances in spontaneously hypertensive rats (SHRs) (4-DAMP [n = 6], ACh [n = 6], ACh + 4-DAMP [n = 6]). Changes in (c) SBP and (d) DBP after oral administration of ACh (10−8 mol/kg BW) in SHRs with vagotomy or sham operation (vagotomy [n = 3], sham [n = 3]). BP shown in (a–d) was measured using the tail-cuff method. Changes in plasma (e) stable isotope-labeled ACh (d9-ACh, N,N,N-trimethyl-d9-acetylcholine) and (f) d9-choline (N,N,N-trimethyl-d9-choline) concentrations after oral administration of d9-ACh (10−6 mol/kg BW) or pure water as a control (d9-ACh [n = 5], control [n = 6]). Each data point and error bar represents the mean ± standard error. Data from the receptor inhibitory test were analyzed by one-way analysis of variance, followed by Tukey’s test. * p < 0.05, ** p < 0.01 versus 4-DAMP group, # p < 0.05, ## p < 0.01 versus ACh + 4-DAMP group. The data from…