The Effects of Rilmenidine and Perindopril on Arousal Blood Pressure during 24 Hour Recordings in SHR

<div><p>The surge in arterial pressure during arousal in the waking period is thought to be largely due to activation of the sympathetic nervous system. In this study we compared in SHR the effects of chronic administration of the centrally acting sympatholytic agent rilmenidine with an angiotensin converting enzyme inhibitor perindopril on the rate of rise and power of the surge in mean arterial pressure (MAP) that occurs with arousal associated with the onset of night. Recordings were made using radiotelemetry in 17 adult SHR before and after treatment with rilmenidine (2mg/kg/day), perindopril (1mg/kg/day) or vehicle in the drinking water for 2 weeks. Rilmenidine reduced MAP by 7.2 ± 1.7mmHg while perindopril reduced MAP by 19 ± 3mmHg. Double logistic curve fit analysis showed that the rate and power of increase in systolic pressure during the transition from light to dark was reduced by 50% and 65%, respectively, but had no effect on diastolic pressure. Rilmenidine also reduced blood pressure variability in the autonomic frequency in the active period as assessed by spectral analysis which is consistent with reduction in sympathetic nervous system activity. Perindopril had no effect on the rate or power of the arousal surge in either systolic or diastolic pressure. These results suggest that the arousal induced surge in blood pressure can largely be reduced by an antihypertensive agent that inhibits the sympathetic nervous system and that angiotensin converting enzyme inhibition, while effective in reducing blood pressure, does not alter the rate or power of the surge associated with arousal.</p></div

Average double logistic fitted curves showing the circadian variation of systolic and diastolic blood pressure, heart rate and behavioural activity over a 24-hour period from 11 SHR before (open circles) and after (filled circles) treatment with vehicle for 2 weeks.

<p>Curves were constructed using the average parameters of double-logistic curve fitting procedure. Error bars indicate SEM of hourly averages.</p

Average results from the circadian analysis of 24-hour blood pressure measurements in rats treated with Vehicle.

<p>Average results from the circadian analysis of 24-hour blood pressure measurements in rats treated with Vehicle.</p

Average results from the circadian analysis of 24-hour blood pressure measurements in rats treated with rilmenidine.

<p>Average results from the circadian analysis of 24-hour blood pressure measurements in rats treated with rilmenidine.</p

Average results from the circadian analysis of 24-hour blood pressure measurements in rats treated with Perindopril.

<p>Average results from the circadian analysis of 24-hour blood pressure measurements in rats treated with Perindopril.</p

Baseline levels of variables in wild type and cationic amino acid transporter-1 overexpressing mice in the 1-h periods immediately prior to stress tests.

<p>Data are mean ± SEM (<i>n</i> = 5–7).</p><p>* <i>P</i> ≤ 0.01 for obese compared with lean mice within the same genotype. <i>P</i> values were derived from un-paired <i>t</i>-tests. WT = wild type mice, CAT+ = endothelial CAT1 overexpressing mice, MAP = mean arterial pressure, HR = heart rate.</p><p>Baseline levels of variables in wild type and cationic amino acid transporter-1 overexpressing mice in the 1-h periods immediately prior to stress tests.</p

Responses to restraint stress in lean and obese mice.

<p>Left and middle panels: Each symbol represents mean values averaged across a 30-s period. Dotted lines represent the time point at which the stress stimulus was applied to mice. Data are mean ± SEM. Right panel: Bar graphs represent absolute changes from baseline in MAP, HR and locomotor activity in response to 5-min restraint stress in mice fed a normal (open bars) or a high fat diet (closed bars). Data are mean difference ± SE of the difference (<i>n</i> = 5–7). ** <i>P</i> < 0.01 for obese <i>vs</i> lean mice within the same genotype. Abbreviations are as for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131424#pone.0131424.g002" target="_blank">Fig 2</a>.</p

Responses to the ganglionic blocker pentolinium in lean and obese wild type and endothelial CAT1 overexpressing mice.

<p>Left and middle panels: Each symbol represents mean values averaged across a 5 min period. The dotted line represents the time point at which pentolinium (5 mg/kg, i.p.) was administered and the shaded areas represent the period analysed for between-group comparisons of the effects of pentolinium. Data are mean ± SEM. Right panel: Histograms represent the average of absolute changes in variables in response to pentolinium. Data are mean difference ± SE of the difference (<i>n</i> = 5–7).* <i>P</i> < 0.05 for obese <i>vs</i> lean mice within the same genotype. WT = wild type mice, CAT+ = endothelial CAT1 overexpressing mice, MAP = mean arterial pressure, HR = heart rate.</p

Responses to shaker stress in lean and obese mice.

<p>Left and middle panels: Each symbol represents mean values averaged across a 30-s period. Dotted line represents the time point at which stress stimulus was applied to mice. Data are mean ± SEM. Right panel: Bar graphs represent absolute changes from baseline in MAP, HR and locomotor activity in response to 5-min shaker stress in mice fed a normal (open bars) or a high fat diet (closed bars) (<i>n</i> = 5–7). Data are mean difference ± SE of the difference (<i>n</i> = 5–7). *** <i>P</i> < 0.001 and ** <i>P</i> < 0.01 for obese <i>vs</i> lean mice within the same genotype. # <i>P</i> < 0.001 lean CAT+ mice <i>vs</i> lean WT mice. Abbreviations are as for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131424#pone.0131424.g002" target="_blank">Fig 2</a>.</p

Effects of stress on systolic and diastolic arterial pressure in lean mice.

<p>Data are mean ± SEM (<i>n</i> = 5–7).</p><p>** <i>P</i> ≤ 0.01</p><p>*** <i>P</i> ≤ 0.001 for CAT+ compared with WT mice</p><p>WT = wild type mice, CAT+ = endothelial CAT1 overexpressing mice, SAP = systolic arterial pressure, DAP = diastolic arterial pressure</p><p>Effects of stress on systolic and diastolic arterial pressure in lean mice.</p