Seymour A A, Abboa-Offei B, Asaad M M, Rogers W L
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, NJ 08543-4000.
Can J Physiol Pharmacol. 1991 Oct;69(10):1609-17. doi: 10.1139/y91-238.
The potent neutral endopeptidase inhibitor SQ 28,603 (N-(2-(mercaptomethyl)-1-oxo-3-phenylpropyl)-beta-alanine) significantly increased excretion of sodium from 4.9 +/- 2.3 to 14.3 +/- 2.1 muequiv./min and cyclic 3',5'-guanosine monophosphate from 118 +/- 13 to 179 +/- 18 pmol/min after intravenous administration of 300 mumol/kg (approximately 80 mg/kg) in conscious female cynomolgus monkeys. SQ 28,603 did not change blood pressure or plasma atrial natriuretic peptide concentrations in the normal monkeys. In contrast, 1-h infusions of 3, 10, or 30 pmol.kg-1.min-1 of human atrial natriuretic peptide lowered blood pressure by -3 +/- 4, -9 +/- 4, and -27 +/- 3 mmHg (1 mmHg = 133.322 Pa), increased cyclic guanosine monophosphate excretion from 78 +/- 11 to 90 +/- 6, 216 +/- 33, and 531 +/- 41 pmol/min, and raised plasma atrial natriuretic peptide from 7.2 +/- 0.7 to 21 +/- 4, 62 +/- 12, and 192 +/- 35 fmol/mL without affecting sodium excretion. In monkeys receiving 10 pmol.kg-1.min-1 of atrial natriuretic peptide, 300 mumol/kg of SQ 28,603 reduced mean arterial pressure by -13 +/- 5 mmHg and increased sodium excretion from 6.6 +/- 3.2 to 31.3 +/- 6.0 muequiv./min, cyclic guanosine monophosphate excretion from 342 +/- 68 to 1144 +/- 418 pmol/min, and plasma atrial natriuretic peptide from 124 +/- 8 to 262 +/- 52 fmol/mL. In conclusion, SQ 28,603 stimulated renal excretory function in conscious monkeys, presumably by preventing the degradation of atrial natriuretic peptide by neutral endopeptidase.
强效中性内肽酶抑制剂SQ 28,603（N-(2-(巯基甲基)-1-氧代-3-苯基丙基)-β-丙氨酸）在清醒雌性食蟹猴静脉注射300 μmol/kg（约80 mg/kg）后，显著增加了钠排泄量，从4.9±2.3增加到14.3±2.1 μeq/分钟，环磷酸鸟苷从118±13增加到179±18 pmol/分钟。SQ 28,603在正常猴子中未改变血压或血浆心钠素浓度。相比之下，以3、10或30 pmol·kg-1·min-1的速率静脉输注人的心钠素1小时，可使血压分别降低-3±4、-9±4和-27±3 mmHg（1 mmHg = 133.322 Pa），使环磷酸鸟苷排泄量从78±11增加到90±6、216±33和531±41 pmol/分钟，并使血浆心钠素从7.2±0.7增加到21±4、62±12和192±35 fmol/mL，而不影响钠排泄。在接受10 pmol·kg-1·min-1心钠素的猴子中，300 μmol/kg的SQ 28,603使平均动脉压降低-13±5 mmHg，并使钠排泄量从6.6±3.2增加到31.3±6.0 μeq/分钟，环磷酸鸟苷排泄量从342±68增加到1144±418 pmol/分钟，血浆心钠素从124±8增加到262±52 fmol/mL。总之，SQ 28,603可能通过防止中性内肽酶降解心钠素，刺激了清醒猴子的肾脏排泄功能。
