Kopp U C, Cicha M Z, Farley D M, Smith L A, Dixon B S
Department of Internal Medicine, University of Iowa College of Medicine, and Department of Veterans Affairs Medical Center, Iowa City 52242, USA.
Hypertension. 1998 Mar;31(3):815-22. doi: 10.1161/01.hyp.31.3.815.
In normotensive rats, increased renal pelvic pressure stimulates the release of prostaglandin E and substance P, which in turn leads to an increase in afferent renal nerve activity (ARNA) and a contralateral natriuresis, a contralateral inhibitory renorenal reflex. In spontaneously hypertensive rats (SHR), increasing renal pelvic pressure failed to increase afferent renal nerve activity. The inhibitory nature of renorenal reflexes indicates that impaired renorenal reflexes could contribute to increased sodium retention in SHR. Phorbol esters, known to activate protein kinase C, increase afferent renal nerve activity in Wistar-Kyoto rats (WKY) but not in SHR. We examined the mechanisms involved in the impaired responses to renal sensory receptor activation in SHR. The phorbol ester 4beta-phorbol 12,13-dibutyrate increased renal pelvic protein kinase C activity similarly in SHR and WKY. Increasing renal pelvic pressure increased afferent renal nerve activity in WKY (27+/-2%) but not in SHR. Renal pelvic release of prostaglandin E increased similarly in WKY and SHR, from 0.8+/-0.1 to 2.0+/-0.4 ng/min and 0.7+/-0.1 to 1.4+/-0.2 ng/min. Renal pelvic release of substance P was greater (P<.01) in WKY, from 16.3+/-3.8 to 41.8+/-7.4 pg/min, than in SHR, from 9.9+/-1.7 to 17.0+/-3.2 pg/min. In WKY, renal pelvic administration of substance P at 0.8, 4, and 20 microg/mL increased ARNA 382+/-69, 750+/-233, and 783+/-124% second (area under the curve of afferent renal nerve activity versus time). In SHR, substance P at 0.8 to 20 microg/mL failed to increase ARNA. These findings demonstrate that the impaired afferent renal nerve activity response to increased renal pelvic pressure is related to decreased release of substance P and/or impaired activation of substance P receptors.
在血压正常的大鼠中，肾盂压力升高会刺激前列腺素E和P物质的释放，进而导致肾传入神经活动（ARNA）增加以及对侧利钠，即对侧抑制性肾-肾反射。在自发性高血压大鼠（SHR）中，增加肾盂压力未能增加肾传入神经活动。肾-肾反射的抑制特性表明，肾-肾反射受损可能导致SHR钠潴留增加。已知能激活蛋白激酶C的佛波酯可增加Wistar-Kyoto大鼠（WKY）的肾传入神经活动，但对SHR无效。我们研究了SHR中对肾感觉受体激活反应受损的机制。佛波酯4β-佛波醇12,13-二丁酸酯在SHR和WKY中同样增加了肾盂蛋白激酶C的活性。增加肾盂压力可增加WKY的肾传入神经活动（27±2%），但对SHR无效。WKY和SHR中肾盂前列腺素E的释放同样增加，分别从0.8±0.1 ng/min增加到2.0±0.4 ng/min以及从0.7±0.1 ng/min增加到1.4±0.2 ng/min。WKY中肾盂P物质的释放量（从16.3±3.8 pg/min增加到41.8±7.4 pg/min）比SHR（从9.9±；1.7 pg/min增加到17.0±3.2 pg/min）更大（P<0.01）。在WKY中，肾盂给予0.8、4和20 μg/mL的P物质可使ARNA分别增加382±69%、750±233%和783±124%（肾传入神经活动曲线下面积与时间）。在SHR中，0.8至20 μg/mL的P物质未能增加ARNA。这些发现表明，肾传入神经活动对肾盂压力升高的反应受损与P物质释放减少和/或P物质受体激活受损有关。
