Charles C J, Nicholls M G, Rademaker M T, Richards A M
Cardioendocrine Research Group, Christchurch School of Medicine, PO Box 4345, Christchurch, New Zealand.
Am J Physiol Regul Integr Comp Physiol. 2001 Dec;281(6):R1887-94. doi: 10.1152/ajpregu.2001.281.6.R1887.
The role of adrenomedullin (ADM) in volume and pressure homeostasis remains undefined. Accordingly, we compared the biological responses to infusions of ADM and nitroprusside (NP; matched for reduction of arterial pressure) and assessed their effects on responses to ANG II and norepinephrine in eight conscious sheep. During matched falls in arterial pressure (8-10 mmHg, both P < 0.001) ADM and NP induced similar increases in heart rate. ADM increased cardiac output (P < 0.001), and the fall in calculated peripheral resistance was greater with ADM than NP (P = 0.013). ADM infusions raised plasma ADM levels (P < 0.001), plasma renin activity (P = 0.001), and ANG II (P < 0.001) but tended to blunt any concurrent rise in aldosterone compared with NP (P = 0.056). ADM maintained both urine flow (P < 0.001) and sodium excretion (P = 0.01) compared with falls observed with NP. ADM attenuated the vasopressor actions of exogenous ANG II (P = 0.006) but not norepinephrine. In addition, ADM antagonized the ANG II-induced rise in plasma aldosterone (P < 0.001). In conclusion, ADM induces a different spectrum of hemodynamic, renal, and endocrine actions to NP. These results clarify mechanisms by which ADM might contribute to volume and pressure homeostasis.
肾上腺髓质素（ADM）在容量和压力稳态中的作用尚不清楚。因此，我们比较了八只清醒绵羊对输注ADM和硝普钠（NP；动脉压降低程度匹配）的生物学反应，并评估了它们对外源性血管紧张素II（ANG II）和去甲肾上腺素反应的影响。在动脉压匹配下降期间（均为8 - 10 mmHg，P均< 0.001），ADM和NP引起相似的心率增加。ADM增加心输出量（P < 0.001），且与NP相比，ADM使计算出的外周阻力下降幅度更大（P = 0.013）。输注ADM使血浆ADM水平升高（P < 0.001）、血浆肾素活性升高（P = 0.001）以及ANG II升高（P < 0.001），但与NP相比，ADM倾向于减弱醛固酮同时出现的升高（P = 0.056）。与NP导致的尿量减少相比，ADM维持了尿流量（P < 0.001）和钠排泄（P = 0.01）。ADM减弱了外源性ANG II的升压作用（P = 0.006），但未减弱去甲肾上腺素的升压作用。此外，ADM拮抗ANG II诱导的血浆醛固酮升高（P < 0.001）。总之，ADM诱导的血流动力学、肾脏和内分泌作用谱与NP不同。这些结果阐明了ADM可能有助于容量和压力稳态的机制。
