Loutzenhiser R, Epstein M
Nephrology Section, Veterans Administration Medical Center, Miami, Fla.
Am J Nephrol. 1987;7 Suppl 1:7-16. doi: 10.1159/000167536.
Theoretical considerations suggest that the renal response to calcium antagonists may vary depending on the factors influencing basal vascular tone. Studies were conducted using the isolated perfused rat kidney to determine the response to calcium antagonists under conditions in which the determinants of renal vascular tone were accurately defined. With this model, calcium antagonists elicit vasodilation only in the presence of a vasoconstrictor. In this setting, however, the degree of vasodilation elicited depends on the nature of the vasoconstrictor employed. Thus, the reduction in renal perfusate flow (RPF) elicited by KCl-induced depolarization was completely reversed by the calcium antagonist, nitrendipine. In contrast, identical levels of vasoconstriction elicited by norepinephrine or angiotensin II were only partially reversed, suggesting that these agonists activate the renal vasculature by mechanisms that are more complex than membrane depolarization. Examination of the response of glomerular filtration rate (GFR) revealed that in the presence of norepinephrine and angiotensin II, nitrendipine exerted a preferential augmentation of GFR. Thus, concentrations that produced only modest effects on RPF increased GFR to levels equal to or exceeding control values. This selective augmentation of GFR did not occur during the renal vasoconstriction elicited by KCl. It is proposed that renal microvessels exhibit regional heterogeneity in regard to activation mechanisms and sensitivity to calcium antagonists. Calcium antagonists may selectively attenuate agonist-induced vasoconstriction of preglomerular vessels.
理论上的考虑表明，肾脏对钙拮抗剂的反应可能会因影响基础血管张力的因素而有所不同。研究采用离体灌注大鼠肾脏，以确定在肾脏血管张力决定因素被准确定义的条件下对钙拮抗剂的反应。利用该模型，钙拮抗剂仅在存在血管收缩剂的情况下才会引起血管舒张。然而，在这种情况下，所引起的血管舒张程度取决于所使用的血管收缩剂的性质。因此，由氯化钾诱导的去极化所引起的肾灌注液流量（RPF）的降低被钙拮抗剂尼群地平完全逆转。相比之下，由去甲肾上腺素或血管紧张素II引起的相同程度的血管收缩仅被部分逆转，这表明这些激动剂通过比膜去极化更复杂的机制激活肾血管系统。对肾小球滤过率（GFR）反应的检查显示，在存在去甲肾上腺素和血管紧张素II的情况下，尼群地平对GFR有优先增强作用。因此，对RPF仅产生适度影响的浓度可将GFR提高到等于或超过对照值的水平。在氯化钾引起的肾血管收缩过程中，并未出现这种对GFR的选择性增强。有人提出，肾微血管在激活机制和对钙拮抗剂的敏感性方面表现出区域异质性。钙拮抗剂可能会选择性地减弱激动剂诱导的肾小球前血管的血管收缩。
