El-Mas M M
Department of Pharmacology, Faculty of Pharmacy, University of Alexandria, Egypt.
J Cardiovasc Pharmacol. 1998 Jun;31(6):869-75. doi: 10.1097/00005344-199806000-00010.
Our previous studies showed that the hypotensive effect of clonidine is enhanced in rats with surgically eliminated aortic baroafferents. In this study, we investigated whether this effect of clonidine is related to facilitation of baroreceptor control of reflex bradycardia. The effects of clonidine on blood pressure (BP), heart rate (HR), and baroreflex-mediated decreases in HR (baroreflex sensitivity, BRS) were studied in conscious aortic barodenervated (ABD) and sham-operated (SO) rats. The slope of the baroreflex curve relating increments in mean arterial pressure (MAP) induced by phenylephrine to corresponding baroreflex-mediated bradycardic responses was taken as an index of BRS. ABD but not the sham operation caused immediate and significant (p < 0.05) increases in BP and HR and an impairment of BRS. Two days after ABD, these parameters, except the BRS, subsided to near control levels. Starting from similar baseline values of BP and HR, clonidine (30 microg/kg, i.v.) elicited significantly (p < 0.05) greater decreases in MAP in conscious ABD rats compared with SO rats (-23 +/- 2 mm Hg vs. -7 +/- 2 mm Hg). The enhanced hypotensive effect of clonidine in ABD rats was associated with a significant reduction in baroreceptor-mediated reflex bradycardic responses to increments in BP evoked by phenylephrine. The slope of the baroreflex curves that represented the BRS showed approximately 40% reduction after treatment with clonidine (baseline BRS, -1.2 +/- 0.06 beats/min/mm Hg; clonidine, -0.73 +/- 0.07 beats/min/mm Hg). On the other hand, a threefold lower decrease in BP by clonidine in SO rats was not associated with any alteration in BRS. These findings support the hypothesis that aortic baroreceptors exert a tonically active restraining influence on centrally mediated hypotension. More important, the results do not favor a role for facilitation of baroreflexes in the enhanced hypotensive effect of clonidine in denervated rats.
我们之前的研究表明,在手术消除主动脉压力感受器传入神经的大鼠中,可乐定的降压作用增强。在本研究中,我们调查了可乐定的这种作用是否与压力感受器对反射性心动过缓的控制促进有关。在清醒的主动脉去神经支配(ABD)大鼠和假手术(SO)大鼠中,研究了可乐定对血压(BP)、心率(HR)以及压力反射介导的HR降低(压力反射敏感性,BRS)的影响。将去氧肾上腺素诱导的平均动脉压(MAP)升高与相应的压力反射介导的心动过缓反应之间的压力反射曲线斜率作为BRS的指标。ABD而非假手术导致BP和HR立即显著升高(p<0.05)以及BRS受损。ABD后两天,除BRS外,这些参数恢复到接近对照水平。从相似的BP和HR基线值开始,与SO大鼠相比,可乐定(30μg/kg,静脉注射)在清醒的ABD大鼠中引起的MAP降低显著更大(p<0.05)(-23±2mmHg对-7±2mmHg)。可乐定在ABD大鼠中增强的降压作用与压力感受器介导的对去氧肾上腺素诱发的BP升高的反射性心动过缓反应显著降低有关。代表BRS的压力反射曲线斜率在可乐定治疗后显示降低约40%(基线BRS,-1.2±0.06次/分钟/mmHg;可乐定,-0.73±0.07次/分钟/mmHg)。另一方面,可乐定在SO大鼠中引起的BP降低幅度低三倍与BRS的任何改变无关。这些发现支持以下假设:主动脉压力感受器对中枢介导的低血压发挥持续的主动抑制作用。更重要的是,结果不支持压力反射促进在去神经大鼠中可乐定增强的降压作用中起作用。