Stickland Michael K, Miller Jordan D, Smith Curtis A, Dempsey Jerome A
John Rankin Laboratory of Pulmonary Medicine, University of Wisconsin, Madison, WI, USA.
Circ Res. 2007 May 11;100(9):1371-8. doi: 10.1161/01.RES.0000266974.84590.d2. Epub 2007 Apr 12.
Previous work has shown sensitization of carotid chemoreceptor (CC) responsiveness during exercise as well as in chronic heart failure (CHF). Accordingly, we hypothesized that the CCs contribute to the sympathetic restraint of skeletal muscle blood flow during exercise and CHF. We examined the effect of transient CC inhibition on total (Con(T)) and hindlimb (Con(L)) conductance, and blood pressure at rest and during exercise (2.5 miles per hour, 5% grade) in chronically instrumented dogs. Via a carotid arterial catheter, CCs were inhibited using dopamine (5 to 10 microg/kg) or hyperoxic lactated Ringer's solution. Although vasodilation did not occur with CC inhibition in resting healthy dogs, CC inhibition during exercise caused an immediate vasodilatory response (increase in Con(T) and Con(L) and decrease in blood pressure). When comparing the peak Con(L) response from CC inhibition versus alpha-adrenergic blockade (phentolamine), we found that the CCs accounted for approximately one-third of the total sympathetic restraint during exercise. CHF was then induced by chronic rapid cardiac pacing and characterized by impaired cardiac function, enhanced chemosensitivity, and greater sympathetic restraint at rest and during exercise. In contrast to healthy dogs, CC inhibition in resting CHF dogs produced vasodilation, whereas a similar vasodilatory response was observed during exercise in CHF as compared with healthy dogs. The vasodilation following CC inhibition during exercise and in CHF was abolished with alpha-adrenergic blockade and was absent in healthy exercising animals after carotid body denervation. These results establish an important role for the CCs in cardiovascular control in the healthy animal during exercise and in the CHF animal both at rest and during exercise.
先前的研究表明,运动期间以及慢性心力衰竭(CHF)时颈动脉化学感受器(CC)的反应性会增强。因此,我们推测CC在运动和CHF期间对骨骼肌血流的交感神经抑制作用中发挥作用。我们研究了在长期植入仪器的犬中,短暂抑制CC对静息和运动(每小时2.5英里,坡度5%)时总(Con(T))和后肢(Con(L))电导以及血压的影响。通过颈动脉导管,使用多巴胺(5至10微克/千克)或高氧乳酸林格液抑制CC。虽然在静息健康犬中抑制CC未引起血管舒张,但运动期间抑制CC会导致立即的血管舒张反应(Con(T)和Con(L)增加,血压降低)。当比较抑制CC与α-肾上腺素能阻断(酚妥拉明)时Con(L)的峰值反应时,我们发现CC在运动期间约占总交感神经抑制作用的三分之一。然后通过慢性快速心脏起搏诱导CHF,其特征为心功能受损、化学敏感性增强以及静息和运动时更大的交感神经抑制。与健康犬不同,静息CHF犬抑制CC会产生血管舒张,而与健康犬相比,CHF犬运动期间观察到类似的血管舒张反应。运动期间和CHF时抑制CC后的血管舒张反应被α-肾上腺素能阻断消除,并且在颈动脉体去神经支配后的健康运动动物中不存在。这些结果表明CC在健康动物运动期间以及CHF动物静息和运动时的心血管控制中起重要作用。