Montañés I, Flores O, Eleno N, López-Novoa J M
Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Salamanca, Spain.
Can J Physiol Pharmacol. 1994 Nov;72(11):1294-8. doi: 10.1139/y94-185.
The purpose of the present study was to assess in rats the prevention by two enantiomers of a new dihydropyridine derivative (pranedipine) (called S12967 for the dextrogyre (+) and S12968 for the levogyre (-) molecules) of the renal and cardiovascular effects induced by endothelin-1. The injection of endothelin-1 (1 nmol/kg body weight) induced a sharp and transient decrease in urine flow, sodium and potassium excretion, glomerular filtration rate, renal plasma flow, and renal blood flow, a significant increase in renal vascular resistance, and a small but significant increase in arterial pressure. Treatment with S12968 alone (0.3 mg/kg) induced a 2.5-fold increase in urine flow and potassium excretion and a 4.5-fold increase in sodium excretion. Pretreatment with S12968 completely blocked the endothelin-1 induced increase in arterial pressure, did not affect the acute effect of endothelin-1 on urine flow, sodium and potassium excretion, filtration rate, and renal blood flow, but blunted the effect on renal vascular resistance. Administration of S12967 alone (1 mg/kg) did not induce changes in either renal function or arterial pressure. In S12967-treated animals, endothelin-1 also induced a transient increase in arterial pressure nad renal vascular resistance but failed to change renal function in a significant manner. In summary, the above reported experiments show that at the higher, nonhypotensive doses, the levogyre enantiomer (S12968) of a new dihydropyridine derivative (pranedipine) completely prevented the hypertensive effect of endothelin 1, and partially prevented the effect of endothelin-1 on renal vascular resistance. The dextrogyre enantiomer (S12967) had almost no effect on either mean arterial pressure or renal vascular resistance but completely blocked the endothelin-1-induced decrease in urine flow and urinary sodium excretion.
本研究的目的是在大鼠中评估一种新的二氢吡啶衍生物（普拉地平）的两种对映体（右旋（+）分子称为S12967，左旋（-）分子称为S12968）对内皮素-1诱导的肾脏和心血管效应的预防作用。注射内皮素-1（1 nmol/kg体重）导致尿流量、钠和钾排泄、肾小球滤过率、肾血浆流量和肾血流量急剧且短暂下降，肾血管阻力显著增加，动脉压小幅但显著升高。单独用S12968（0.3 mg/kg）治疗使尿流量和钾排泄增加2.5倍，钠排泄增加4.5倍。用S12968预处理可完全阻断内皮素-1诱导的动脉压升高，不影响内皮素-1对尿流量、钠和钾排泄、滤过率及肾血流量的急性作用，但可减弱其对肾血管阻力的作用。单独给予S12967（1 mg/kg）对肾功能或动脉压均无影响。在接受S12967治疗的动物中，内皮素-1也导致动脉压和肾血管阻力短暂升高，但未显著改变肾功能。总之，上述实验表明，在较高的非降压剂量下，一种新的二氢吡啶衍生物（普拉地平）的左旋对映体（S12968）可完全预防内皮素-1的高血压作用，并部分预防内皮素-1对肾血管阻力的作用。右旋对映体（S12967）对平均动脉压或肾血管阻力几乎无影响，但可完全阻断内皮素-1诱导的尿流量和尿钠排泄减少。
