心房钠尿肽的中枢性心血管和肾效应

在麻醉大鼠观察了颈动脉、脊髓蛛网膜下腔和侧脑室内注射心房钠尿肽(Atrial natri-uretic peptide,ANP)后,血压,心率或/和尿量、尿钠和尿钾的变化,并观察了 ANP 对血管紧张素Ⅱ(AGⅡ)中枢效应的影响。结果如下:(1)在大鼠头部交叉循环条件下,经受血鼠颈总动脉内注射α-人心房钠尿多肽(α-human atrial natriurctic polypeptide,α-hANP)(15μg/kg)后,受血鼠平均动脉压(MAP)无改变,而供血鼠的 MAP 降低,⊿MAP为-2.4±0.84kPa(-18±6.3mmHg,P<0.05),(2)脊髓蛛网膜下腔注射心房肽,Ⅱ(AtriopeptinⅡ,APⅡ)(5μg/kg)对血压、心率和尿量无明显影响;(3)侧脑室注射 APⅡ(20μg/kg)后血压和心率无显著改变,尿量仅在注射后第30至50min 时显著增加,而尿钠无改变;(4)侧脑室注射 AGⅡ(1μg/kg),血压升高,⊿MAP 为1.3±0.17kPa(10±1.3mmHg,n=10,P<0.001)。注射1h 后,尿量增加106%(P<0.01),尿钠增加642%(P<0.01);(5)事先侧脑室注射 APⅡ(20μg/kg),2min 后再注入 AGⅡ(1μg/kg),AGⅡ的中枢升压效应不受影响,⊿MAP为1.5±0.25kPa(11±1.9mmHg,n=7,P<0.01),而尿量和尿钠的增值明显减小。以上结果表明,ANP 难于透过血脑脑脊血屏障,可能与其分子量较大有关。在静脉注射 ANP 所致降压效应中,似无中枢机制的参与。ANP 对 AGⅡ

CENTRAL CARDIOVASCULAR AND RENAL EFFECTS OF ATRIAL NATRIURETIC PEPTIDE

In 54 anesthetized rats, the changes in arterial blood pressure, heart rate and/or urine volume, urinary sodium excretion were observed following intracarotid, intrathecal and intracerebroventricular (ICV) injection of atrial natriuretic peptide (ANP). The effects of ANP on the central actions of angiotensin II (AG II) were also examined. The results were as follows: (1) In the cross-circulation preparation of rat head, MAP of the recipient was unchanged and that of the donor was decreased in response to the administration of alpha-hANP (15 micrograms/kg) into the carotid artery of the recipient. (2) By injecting AP III (5 micrograms/kg) intrathecally, MAP, HR and urine volume (V) of the rats (n = 7) showed no change. (3) The ICV injection of AP III (20 micrograms/kg) did not result in changes in MAP, HR, and urinary sodium excretion (UNaV), but there was a transient and significant increase in V. (4) ICV injection of AG II (1 microgram/kg) resulted in an increase of MAP by 1.3 +/- 0.17 kPa (10 +/- 1.3 mmHg, n = 10, P less than 0.001), V by 106% (n = 6, P less than 0.01) and UNaV by 642% (P less than 0.01). (5) ICV injection of AP III 2 min prior to the injection of AG II by the same route, the central hypertensive effect induced by AG II was not affected, while the increments in V and UNaV were decreased significantly (P less than 0.05). The results indicate that (1) ANP is incapable of penetrating the blood-brain barrier owing to its large molecular size and therefore, the central mechanism is not involved in the hypotensive effect induced by intravenous injection of ANF and (2) the central diuretic and natriuretic actions of AG II may be markedly inhibited by ICV injection of ANP, thus indicating the existence of some central antagonistic interactions between AG II and ANP.