Golin R, Protasoni G, Wjinmaalen P, Sala C, Monopoli A, Casati C, Zanchetti A, Stella A
Istituto di Clinica Medica Generale e Terapia Medica, University of Milan, Italy.
J Cardiovasc Pharmacol. 1996 Nov;28(5):665-71. doi: 10.1097/00005344-199611000-00009.
To evaluate the interaction between renal nerves, the atrial natriuretic peptide (ANP), and the renin-angiotensin system (RAS), electrical stimulation of renal nerves was performed in spontaneously hypertensive rats (SHR) and in their normotensive controls, Wistar Kyoto rats (WKY), before and after pharmacologic treatment with (a) a neutral endopeptidase inhibitor (NEP-i) to enhance the intrarenal ANP activity; (b) an ACE inhibitor (ACE-i) to block RAS; (c) both NEP-i and ACE-i; and (d) the vehicle of the drugs. Renal nerve stimulation did not change arterial pressure (AP) but reduced renal blood flow (RBF), glomerular filtration rate (GFR), and urinary sodium excretion (UNa+V) in both WKY and SHR. NEP-i treatment in WKY and SHR had no systemic or renal hemodynamic effects but increased GFR and urinary cyclic guanosine monophosphate (GMP) excretion; UNa+V increased (+2.78 +/- 0.31 microEq/min) in WKY, whereas it did not change in SHR (+0.83 +/- 0.79 microEq/min). In both strains, ACE-i treatment reduced AP, increased RBF, and did not change GFR and UNa+V. The combined treatment with NEP-i and ACE-i did not modify the natriuretic effect observed in NEP-i treated WKY (+4.29 +/- 1.25 microEq/min), but it elicited a natriuretic effect in SHR (+3.98 +/- 1.29 microEq/min). Pharmacologic treatment did not change the hemodynamic and excretory responses to renal nerve stimulation in both WKY and SHR. In conclusion, NEP-i treatment increased UNa+V in normotensive rats without changing AP. In hypertensive rats, the natriuretic effect of NEP-i became evident only after block of RAS by ACE-i. Neither NEP-i nor ACE-i, even in combination, could modify the renal responses to sympathetic stimulation.
为评估肾神经、心房利钠肽（ANP）和肾素 - 血管紧张素系统（RAS）之间的相互作用，在自发性高血压大鼠（SHR）及其血压正常的对照Wistar Kyoto大鼠（WKY）中，于药物治疗前后进行肾神经电刺激，药物治疗包括：（a）使用中性内肽酶抑制剂（NEP - i）以增强肾内ANP活性；（b）使用血管紧张素转换酶抑制剂（ACE - i）以阻断RAS；（c）同时使用NEP - i和ACE - i；（d）使用药物载体。肾神经刺激在WKY和SHR中均未改变动脉血压（AP），但降低了肾血流量（RBF）、肾小球滤过率（GFR）和尿钠排泄（UNa + V）。WKY和SHR中的NEP - i治疗对全身或肾脏血流动力学无影响，但增加了GFR和尿环磷酸鸟苷（GMP）排泄；WKY中UNa + V增加（+2.78±0.31微当量/分钟），而SHR中未改变（+0.83±0.79微当量/分钟）。在两种品系中，ACE - i治疗降低了AP，增加了RBF，且未改变GFR和UNa + V。NEP - i和ACE - i联合治疗未改变NEP - i治疗的WKY中观察到的利钠作用（+4.29±1.25微当量/分钟），但在SHR中引发了利钠作用（+3.98±1.29微当量/分钟）。药物治疗未改变WKY和SHR中对肾神经刺激的血流动力学和排泄反应。总之，NEP - i治疗在血压正常的大鼠中增加了UNa + V，而未改变AP。在高血压大鼠中，仅在通过ACE - i阻断RAS后，NEP - i的利钠作用才变得明显。单独或联合使用NEP - i和ACE - i均不能改变肾脏对交感神经刺激的反应。
