Stephens G W, Lieberthal W, Oza N B, Valeri C R, Levinsky N G
Evans Memorial Department of Clinical Research, University Hospital, Boston University Medical Center, Mass.
Ren Physiol Biochem. 1988 Jan-Feb;11(1-2):50-9. doi: 10.1159/000173149.
We have found that arginine vasopressin (AVP) (10 pg/ml) stimulates urinary kallikrein in the isolated erythrocyte perfused rat kidney. (In this model, perfusate flow rate approximates blood flow rates in vivo and morphology is normal.) Urinary kallikrein excretion rose from 6.9 +/- 0.8 to 14.9 +/- 2.4 ng/min 20 min after the addition of AVP to the perfusate, and then fell towards baseline levels over the next 30 min. 1-Desamino-8-D-AVP (8 pg/ml) caused a comparable increase in kallikrein excretion. Prostaglandin synthesis inhibition with indomethacin did not alter the stimulatory effect of AVP on kallikrein excretion. Parathyroid hormone 1-34 (144 ng/ml) and calcitonin (102 ng/ml) also increased urinary kallikrein. Kallikrein excretion rose from 9.1 +/- 2.0 to 24 +/- 4.5 ng/min in response to calcitonin and from 8.3 +/- 1.6 to 43.7 +/- 3.4 ng/min following the addition of parathyroid hormone to the perfusate. Kallikrein was found to accumulate in the perfusate in a linear fashion. Based on the slope of the relationship between perfusate kallikrein and time, the rate of release of kallikrein into the perfusate was estimated to be 0.79 ng/min in control kidneys. The rate of release of kallikrein into the perfusate in kidneys treated with AVP was the same (0.74 ng/min). Thus while kallikrein is released into the perfusate, this process is not influenced by AVP. In conclusion, AVP stimulates release of kallikrein into the urine (but not the perfusate) independently of systemic events. The effect of AVP is not mediated by prostaglandins. This effect of AVP is mediated via stimulation of the V2 receptor and also occurs in response to two other hormones (calcitonin and parathyroid hormone) that are known to stimulate adenyl cyclase in the rat distal nephron.
我们发现，精氨酸加压素（AVP）（10皮克/毫升）可刺激离体红细胞灌注大鼠肾脏中的尿激肽释放酶。（在此模型中，灌注液流速近似于体内血流速度，且形态正常。）向灌注液中添加AVP后20分钟，尿激肽释放酶排泄量从6.9±0.8纳克/分钟升至14.9±2.4纳克/分钟，然后在接下来的30分钟内降至基线水平。1-去氨基-8-D-精氨酸加压素（8皮克/毫升）使激肽释放酶排泄量出现类似增加。用吲哚美辛抑制前列腺素合成并未改变AVP对激肽释放酶排泄的刺激作用。甲状旁腺激素1-34（144纳克/毫升）和降钙素（102纳克/毫升）也可增加尿激肽释放酶。降钙素作用下，激肽释放酶排泄量从9.1±2.0纳克/分钟升至24±4.5纳克/分钟；向灌注液中添加甲状旁腺激素后，激肽释放酶排泄量从8.3±1.6纳克/分钟升至43.7±3.4纳克/分钟。发现激肽释放酶以线性方式在灌注液中蓄积。根据灌注液中激肽释放酶与时间关系的斜率，对照肾脏中激肽释放酶释放到灌注液中的速率估计为0.79纳克/分钟。用AVP处理的肾脏中激肽释放酶释放到灌注液中的速率相同（0.74纳克/分钟）。因此，虽然激肽释放酶释放到灌注液中，但该过程不受AVP影响。总之，AVP独立于全身事件刺激激肽释放酶释放到尿液中（而非灌注液中）。AVP的作用不是由前列腺素介导的。AVP的这种作用是通过刺激V2受体介导的，并且在对另外两种已知可刺激大鼠远端肾单位中腺苷酸环化酶的激素（降钙素和甲状旁腺激素）作出反应时也会发生。
