米兰高血压和正常血压大鼠中心房利钠肽的清除受体

Clearance receptors for atrial natriuretic petide in Milan hypertensive and normotensive rats.

作者信息

Aptel H B, Wannop D W, al-Busada K, Henderson I W

机构信息

Sheffield University, Department of Animal and Plant Sciences, Western Bank, UK.

出版信息

J Hypertens. 1996 Apr;14(4):461-8.

PMID:8761895

Abstract

OBJECTIVE

Renal responses of anaesthetized Milan hypertensive (MHS) and Milan normotensive (MNS) rats to des-[Glu18-Ser19-Gly20-Leu21-Gly22]r atrial natriuretic peptide-4-23 (cANP4-23) a specific ligand for atrial natriuretic petide (ANP) clearance receptors were examined.

METHODS

The peptide was administered intravenously as an initial bolus injection (10 micrograms/kg body weight) followed by constant infusion (1 microgram/min per kg body weight) for 30 min. Glomerular filtration rate, urine flow, sodium excretion and mean blood pressures were measured. Using the same protocol, plasma ANP levels were determined.

RESULTS

Plasma ANP levels were significantly increased in both Milan strains (from 9.5 +/- 1.8 to 23.7 +/- 3.2 fmol/ml in MHS rats and from 9.8 +/- 1.2 to 15.9 +/- 1 fmol/ml in MNS rats). This increase was significantly greater in the MHS than in the MNS rats. The cANP4-23 infusions were diuretic and natriuretic in both strains of rats but despite a greater rise in plasma ANP level, the renal response was attenuated in the MHS compared with that in the MNS rats. Furthermore, the time course differed in that the hypertensive rats had a diuresis of slower onset. During cANP4-23 infusion, the mean blood pressure decrease was greater in the MHS rats, consistent with the fact that phenylephrine-precontracted isolated MHS rat aortae were threefold more sensitive to ANP-induced relaxation than were MNS rat aortae. Displacements of [125l]-rANP by rANP and cANP4-23 in isolated renal glomeruli indicated that MHS rats have similar amounts of cANP receptors but with a higher affinity for cANP than have MNS rats.

CONCLUSION

cANP4-23 infusion increased plasma ANP more in MHS than in MNS rats. Renal responses were attenuated in the MHS rat compared with those in MNS rats. These differential actions cannot be explained in terms of glomerular ANP receptor densities, although aortic ring sensitivities differ between the two strains of rat.

摘要

目的

研究麻醉状态下的米兰高血压大鼠（MHS）和米兰正常血压大鼠（MNS）对去-[Glu18-Ser19-Gly20-Leu21-Gly22]r心钠素-4-23（cANP4-23）的肾脏反应，cANP4-23是心钠素（ANP）清除受体的特异性配体。

方法

该肽通过静脉注射给予初始推注（10微克/千克体重），随后持续输注（1微克/分钟/千克体重）30分钟。测量肾小球滤过率、尿流量、钠排泄和平均血压。使用相同方案测定血浆ANP水平。

结果

两种米兰品系大鼠的血浆ANP水平均显著升高（MHS大鼠从9.5±1.8飞升摩尔/毫升升至23.7±3.2飞升摩尔/毫升，MNS大鼠从9.8±1.2飞升摩尔/毫升升至15.9±1飞升摩尔/毫升）。MHS大鼠的这种升高显著大于MNS大鼠。cANP4-23输注在两种品系大鼠中均具有利尿和利钠作用，但尽管血浆ANP水平升高幅度更大，MHS大鼠的肾脏反应与MNS大鼠相比有所减弱。此外，时间进程有所不同，即高血压大鼠的利尿起效较慢。在cANP4-23输注期间，MHS大鼠的平均血压下降幅度更大，这与苯肾上腺素预收缩的离体MHS大鼠主动脉对ANP诱导的舒张比MNS大鼠主动脉敏感三倍的事实一致。rANP和cANP4-23在离体肾小体中对[125I]-rANP的置换表明，MHS大鼠的cANP受体数量相似，但对cANP的亲和力高于MNS大鼠。