Jones-Dombi T, Churchill P
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Life Sci. 1993;53(20):1531-7. doi: 10.1016/0024-3205(93)90561-g.
There are only a few previous reports of the renal effects of the Ca channel agonist BAY K 8644, and the renin secretory effects in particular are unclear. In the present experiments, isolated rat kidneys were perfused at 120 and 100 mm Hg before and after adding BAY K 8644 to the perfusate (0.05 microM final concentration), and perfusate flow rate, glomerular filtration rate (GFR), urine flow, Na excretion, and renin secretory rate were measured. BAY K 8644 increased renal vascular resistance, as evidence by decreases in perfusate flow and GFR at constant perfusion pressure, and decreased urine flow and Na excretion. Renin secretory rates were 51 +/- 4 versus 23 +/- 3 ng A I hr-1 min-1 at 120 mm Hg (p < 0.01), and 184 +/- 54 versus 38 +/- 14 ng A I hr-1 min-1 at 100 mm Hg (p < 0.01), in the absence versus the presence of BAY K 8644, respectively. Therefore, BAY K 8644 inhibits renin secretion at constant perfusion pressure and blunts the stimulatory effect on renin secretion of decreases in renal perfusion pressure. Collectively, these observations add to the growing evidence that the renin secreting juxtaglomerular cells have voltage-operated Ca channels, that depolarization-induced Ca influx inhibits renin secretion, and that Ca is an inhibitory second messenger in the renin secretory process.
关于钙通道激动剂BAY K 8644对肾脏影响的既往报道仅有几篇，尤其是其对肾素分泌的影响尚不清楚。在本实验中，在灌注液中加入BAY K 8644（终浓度0.05微摩尔）前后，分别以120和100毫米汞柱的压力灌注离体大鼠肾脏，并测量灌注液流速、肾小球滤过率（GFR）、尿流、钠排泄及肾素分泌率。BAY K 8644增加了肾血管阻力，表现为在恒定灌注压力下灌注液流速和GFR降低，同时尿流和钠排泄减少。在120毫米汞柱时，无BAY K 8644与有BAY K 8644时肾素分泌率分别为51±4与23±3纳克AI·小时⁻¹·分钟⁻¹（p<0.01）；在100毫米汞柱时，分别为184±54与38±14纳克AI·小时⁻¹·分钟⁻¹（p<0.01）。因此，BAY K 8644在恒定灌注压力下抑制肾素分泌，并减弱肾灌注压降低对肾素分泌的刺激作用。总体而言，这些观察结果进一步证明了分泌肾素的球旁细胞具有电压门控钙通道，去极化诱导的钙内流抑制肾素分泌，以及钙在肾素分泌过程中是一种抑制性第二信使。
