Seymour A A, Mazack E K
Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania.
Circ Res. 1988 Mar;62(3):506-14. doi: 10.1161/01.res.62.3.506.
The contribution of the renin-angiotensin system to the natriuretic responses to intrarenal infusions of 1, 5, 25, and 125 pmol/kg/min synthetic rat atrial natriuretic peptide 101-126 was determined in one-kidney anesthetized dogs. In vehicle-treated dogs, atrial natriuretic peptide 101-126 increased fractional sodium excretion from 1.8 +/- 0.6% to a peak response of 5.1 +/- 0.9% during infusion of 25 pmol/kg/min. The peptide progressively decreased mean arterial pressure from 110 +/- 5 to 94 +/- 4 mm Hg, renal vascular resistance from 0.40 +/- 0.02 to 0.30 +/- 0.02 mm Hg/ml/min, and arterial plasma renin activity from 4.3 +/- 1.6 to 3.1 +/- 0.8 ng/ml/hr. When the renin-angiotensin system was blocked by 3 mg/kg i.v. enalaprilat, baseline pressure fell to 86 +/- 4 mm Hg, and subsequent infusions of atrial natriuretic peptide 101-126 did not affect fractional sodium excretion. The decreases in blood pressure (from 86 +/- 4 to 76 +/- 4 mm Hg) and in renal vascular resistance (from 0.27 +/- 0.03 to 0.23 +/- 0.02 mm Hg/ml/min) were also ameliorated compared with the control responses. Intravenous infusion of 2.5 ng/kg/min angiotensin II restored mean arterial pressure and potentiated the natriuretic and renal vascular responses to atrial natriuretic peptide 101-126. In two additional groups of anesthetized dogs, enalaprilat did not produce the profound hypotension and did not affect the natriuretic responses to atrial natriuretic peptide 101-126. When renal vascular resistance was elevated by intrarenal infusion of angiotensin II in enalaprilat-treated dogs, the natriuretic response was improved.(ABSTRACT TRUNCATED AT 250 WORDS)
在单肾麻醉犬中,测定了肾素 - 血管紧张素系统对肾内输注1、5、25和125 pmol/kg/分钟合成大鼠心房利钠肽101 - 126的利钠反应的贡献。在给予赋形剂的犬中,心房利钠肽101 - 126在以25 pmol/kg/分钟输注期间,使钠排泄分数从1.8±0.6%增加到峰值反应5.1±0.9%。该肽使平均动脉压从110±5逐渐降至94±4 mmHg,肾血管阻力从0.40±0.02降至0.30±0.02 mmHg/ml/分钟,动脉血浆肾素活性从4.3±1.6降至3.1±0.8 ng/ml/小时。当肾素 - 血管紧张素系统被静脉注射3 mg/kg依那普利拉阻断时,基线血压降至86±4 mmHg,随后输注心房利钠肽101 - 126不影响钠排泄分数。与对照反应相比,血压(从86±4降至76±4 mmHg)和肾血管阻力(从0.27±0.03降至0.23±0.02 mmHg/ml/分钟)的降低也有所改善。静脉输注2.5 ng/kg/分钟血管紧张素II可恢复平均动脉压,并增强对心房利钠肽101 - 126的利钠和肾血管反应。在另外两组麻醉犬中,依那普利拉未产生严重低血压,也不影响对心房利钠肽101 - 126的利钠反应。当在依那普利拉治疗的犬中通过肾内输注血管紧张素II升高肾血管阻力时,利钠反应得到改善。(摘要截短于250字)