Laurent S, Brisac A M, Champeroux P, Lacolley P, Huguet F, Legrand M, Lucet B, Tsoucaris D, Briand V, Schmitt H
Laboratoire de Neuropharmacologie Cardio-Vasculaire et INSERM U228, Paris, France.
Fundam Clin Pharmacol. 1989;3 Suppl:47s-56s. doi: 10.1111/j.1472-8206.1989.tb00474.x.
Intracerebroventricular (i.c.v.) injections of dihydropyridine derivatives calcium channel agonist (BAY K8644) and antagonist (nifedipine, nicardipine, PN 200-110) induced opposite long-lasting changes in blood pressure (BP) in pentobarbital anesthetized spontaneously hypertensive rats (SMR). I.c.v. nifedipine (NIF), nicardipine (NIC), and PN 200-110 decreased mean blood pressure dose-dependently and stereoselectively, (+) NIC and (+) PN being 8 and 3 times more potent than their (-) isomers, respectively. The decrease in BP was due to a withdrawal of the sympathetic tone, since NIF- and NIC-induced falls in BP were suppressed after either hexamethonium (HXM), 6 OHDA or bilateral adrenalectomy. I.c.v. BAY K8644 increased BP dose-dependently. The i.c.v. BAY K8644-induced hypertensive effect was inhibited: a), by NIF and (+) PN but not by (-) PN, therefore probably occurring at central DHP sites; b), by HXM and reserpine, thus probably mediated by an increase in sympathetic tone; c) by i.c.v. methylatropine (MA) while i.v. MA and i.c.v. HXM had no inhibitory effect, thus probably involving central muscarinic sites. In SHR, NIC did not after the K(+)-evoked ACh release but suppressed the BAY K8644-induced increase in ACh release. In anesthetized normotensive control rats (WKY), neither i.c.v. NIF, NIC or BAY increased BP and HR while, in conscious SHR it decreased BP without any change in HR. These data increased BP and HR while, in conscious SHR it decreased BP without any change in HR. These data suggest that central DHP sites may be involved in the cholinergic transmission and may participate in genetic hypertension via sympathetic tone.
向戊巴比妥麻醉的自发性高血压大鼠（SHR）脑室内（i.c.v.）注射二氢吡啶衍生物钙通道激动剂（BAY K8644）和拮抗剂（硝苯地平、尼卡地平、PN 200 - 110）可引起血压（BP）相反的持久变化。脑室内注射硝苯地平（NIF）、尼卡地平（NIC）和PN 200 - 110可剂量依赖性且立体选择性地降低平均血压，（+）NIC和（+）PN的效力分别比其（-）异构体高8倍和3倍。血压降低是由于交感神经张力的减弱，因为六甲铵（HXM）、6 - 羟基多巴胺（6 - OHDA）或双侧肾上腺切除术后，NIF和NIC引起的血压下降受到抑制。脑室内注射BAY K8644可剂量依赖性地升高血压。脑室内注射BAY K8644引起的高血压效应受到抑制：a），被NIF和（+）PN抑制，但不被（-）PN抑制，因此可能发生在中枢二氢吡啶（DHP）位点；b），被HXM和利血平抑制，因此可能由交感神经张力增加介导；c），被脑室内注射甲基阿托品（MA）抑制，而静脉注射MA和脑室内注射HXM没有抑制作用，因此可能涉及中枢毒蕈碱位点。在SHR中，NIC不影响钾离子诱发的乙酰胆碱（ACh）释放，但抑制BAY K8644引起的ACh释放增加。在麻醉的正常血压对照大鼠（WKY）中，脑室内注射NIF、NIC或BAY均不会升高血压和心率，而在清醒的SHR中，它可降低血压且心率无任何变化。这些数据表明，中枢DHP位点可能参与胆碱能传递，并可能通过交感神经张力参与遗传性高血压的发生。
