Paulis L', Lísková S, Pintérová M, Dobesová Z, Kunes J, Zicha J
Cardiovascular Research Center, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Acta Physiol (Oxf). 2007 Dec;191(4):255-66. doi: 10.1111/j.1748-1716.2007.01737.x. Epub 2007 Aug 3.
The relationship between increased sympathetic tone and enhanced activity of L-type voltage-dependent Ca2+ channels (L-VDCC) in spontaneously hypertensive rats (SHR) was studied using in vivo and in vitro approaches.
The effects of acute L-VDCC blockade on sympathetic vasoconstriction or blood pressure (BP) and the contribution of calcium influx to norepinephrine (NE)-induced arterial contraction were investigated in 10-week-old SHR and in age-matched SHR made normotensive by chronic captopril treatment from weaning.
Blood pressure fall occurring after acute ganglionic or L-VDCC blockade was enhanced in SHR. Ganglionic blockade eliminated strain differences in BP response to acute L-VDCC blockade and vice versa, suggesting that enhanced contribution of L-VDCC is responsible for augmented sympathetic vasoconstriction in SHR. Both phasic (dependent on internal calcium stores) and tonic (dependent on calcium influx) contractions to NE were augmented in SHR femoral arteries in vitro. Nifedipine attenuated only tonic contractions but to a larger extent in SHR than in WKY arteries. Nifedipine effect was greater after endothelium removal, which augmented tonic but not phasic contractions after NE. Chronic captopril treatment of SHR prevented hypertension development by suppression of their sympathetic vasoconstriction including its nifedipine-sensitive component, but failed to influence enhanced NE-induced arterial contractions or increased relaxation to nifedipine in vitro.
The contribution of nifedipine-sensitive component to noradrenergic vasoconstriction is enhanced during excessive NE stimulation (increased sympathetic tone of SHR in vivo or supramaximal NE stimulation in vitro). It seems that captopril-induced reduction of central sympathetic tone is able to normalize augmented nifedipine-sensitive vasoconstriction in SHR.
采用体内和体外方法研究自发性高血压大鼠（SHR）交感神经张力增加与L型电压依赖性钙通道（L-VDCC）活性增强之间的关系。
在10周龄的SHR以及从断奶起用慢性卡托普利治疗使其血压正常的年龄匹配的SHR中，研究急性L-VDCC阻断对交感神经血管收缩或血压（BP）的影响，以及钙内流对去甲肾上腺素（NE）诱导的动脉收缩的作用。
急性神经节或L-VDCC阻断后SHR的血压下降增强。神经节阻断消除了BP对急性L-VDCC阻断反应的品系差异，反之亦然，这表明L-VDCC作用增强是SHR交感神经血管收缩增强的原因。在体外，SHR股动脉对NE的相性（依赖于细胞内钙储存）和持续性（依赖于钙内流）收缩均增强。硝苯地平仅减弱持续性收缩，但在SHR中比在WKY动脉中减弱程度更大。去除内皮后硝苯地平的作用更大，去除内皮后NE引起的持续性收缩增强但相性收缩未增强。对SHR进行慢性卡托普利治疗可通过抑制其交感神经血管收缩（包括其对硝苯地平敏感的成分）来预防高血压的发展，但未能影响NE诱导的动脉收缩增强或体外对硝苯地平的舒张反应增加。
在过量NE刺激期间（体内SHR交感神经张力增加或体外超最大NE刺激），硝苯地平敏感成分对去甲肾上腺素能血管收缩的作用增强。似乎卡托普利诱导的中枢交感神经张力降低能够使SHR中增强的硝苯地平敏感血管收缩恢复正常。
