el-Mas M M, Carroll R G, Abdel-Rahman A A
Department of Pharmacology, East Carolina University School of Medicine, Greenville, North Carolina 27858.
J Cardiovasc Pharmacol. 1994 Aug;24(2):184-93.
In a previous study, we showed that centrally mediated hypotensive responses are enhanced in aortic barodenervated (ABD) rats as compared with sham-operated (SO) rats. In the present study, we tested the hypothesis that the high basal total peripheral resistance (TPR) of ABD rats accounts for enhanced hypotensive responses to clonidine in this rat model. Aortic barodenervation resulted in acute increases in blood pressure (BP) and heart rate (HR) in anesthetized rats, associated with significant increases in plasma norepinephrine (NE) levels and TPR; cardiac index (CI) and stroke volume (SV) were not affected. After recovery from anesthesia, conscious ABD rats had significantly increased BP at 3 h after barodenervation; BP returned to SO levels by 48 h even though plasma NE levels and TPR remained significantly increased. On the other hand, CI and SV showed significant reductions, beginning at 3 h, and remained low throughout the postdenervation period (48 h); the reduction in CI offset the increase in TRP and may therefore account for the restoration of BP of ABD rats to normal levels. Beginning at similar baseline BP values, cumulative intracisternal (i.c.) doses of clonidine (0.02-2.5 micrograms) elicited greater decreases in BP and plasma NE levels in conscious ABD as compared with SO rats. These responses were centrally mediated because systemic administration of 0.12 micrograms clonidine, a dose that elicited near maximal hypotensive response after i.c. administration, affected neither BP nor plasma NE levels. Contrary to the hypothesis, the hypotensive effect of clonidine in ABD rats resulted exclusively from a reduction in CO (owing to reductions in both HR and SV) because TPR was not affected. These findings suggest that (a) in ABD rats, a reduction in CO offsets a sustained sympathetically mediated elevation in TPR and restores BP to normal levels; and (b) an enhanced hypotensive response to clonidine in ABD as compared with SO rats cannot be accounted for by a higher basal TRP but rather by elicitation of greater reductions in CO through a centrally mediated sympathoinhibitory action.
在先前的一项研究中，我们发现与假手术（SO）大鼠相比，主动脉去神经支配（ABD）大鼠的中枢介导的降压反应增强。在本研究中，我们检验了这样一个假设，即ABD大鼠较高的基础总外周阻力（TPR）是该大鼠模型中对可乐定降压反应增强的原因。主动脉去神经支配导致麻醉大鼠的血压（BP）和心率（HR）急性升高，同时血浆去甲肾上腺素（NE）水平和TPR显著升高；心脏指数（CI）和每搏输出量（SV）未受影响。麻醉恢复后，清醒的ABD大鼠在去神经支配后3小时血压显著升高；尽管血浆NE水平和TPR仍显著升高，但血压在48小时恢复到SO大鼠的水平。另一方面，CI和SV从3小时开始显著降低，并在去神经支配后的整个时期（48小时）一直保持较低水平；CI的降低抵消了TRP的升高，因此可能是ABD大鼠血压恢复到正常水平的原因。从相似的基线血压值开始，与SO大鼠相比，清醒的ABD大鼠经脑池内（i.c.）累积给予可乐定（0.02 - 2.5微克）后，血压和血浆NE水平的降低幅度更大。这些反应是由中枢介导的，因为全身给予0.12微克可乐定（该剂量在脑池内给药后可引起接近最大的降压反应）对血压和血浆NE水平均无影响。与该假设相反，可乐定对ABD大鼠的降压作用完全是由于心输出量（CO）降低（由于HR和SV均降低），因为TPR未受影响。这些发现表明：（a）在ABD大鼠中，CO的降低抵消了交感神经介导的TPR持续升高，并使血压恢复到正常水平；（b）与SO大鼠相比，ABD大鼠对可乐定的降压反应增强不能用更高的基础TRP来解释，而是通过中枢介导的交感神经抑制作用引起CO更大幅度的降低来解释。
