Complex haemodynamic changes in vivo after adrenomedullin administration in rats

Journal of Clinical and Basic Cardiology 2001; 4 (1): 79-82

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Keywords: adrenomedullin,  pulmonale Hypertonie,  adrenomedullin,  pulmonary hypertension

Adrenomedullin (ADM) is a peptide that has potent vasodilatory effect in several vascular beds. Its effect on the haemodynamics of the systemic-pulmonary circulation is unknown. We studied the kinetics of ADM action in rats in vivo with pulmonary hypertension. Sprague-Dawley rats, 6 weeks old (280?340 g), were divided into control (n = 5), MCT (n = 6) and ADM (n = 6) groups and received a single intraperitoneal dose of vehicle, monocrotaline (60 mg/kg b.wt.) and ADM(1?50) (3 nmol/kg b.wt.) respectively. Three weeks later, systemic (Ps) and direct pulmonary arterial mean pressures (Pa, mmHg) were measured after ADM administration (6.6 pmol) every 2 min for up to 18 min. Ps declined at 2 min in MCT and ADM groups (79.4 ± 3.5 to 76.6 ± 3.8 and 63.7 ± 5.5 to 58.7 ± 1.1 respectively), but was delayed until 4 min in the Control group (68.5 ± 1.4 to 61.8 ± 1.9). There were no significant differences in Ps 6 to 12 min following ADM administration between the groups. At 12 min, there was a 30.8 % (54.9 ± 4.0) decrease in MCT group compared to baseline (p = 0.0005). Similar kinetic patterns were observed in Pa in all three groups with a marked decrease (28.4 %) from 18.0 ± 1.0 to 12.9 ± 0.7, p = 0.0007, in MCT group after 12 min. The hypotensive effect of ADM in the Pa was shorter (8 min) in the ADM pretreated animals compared to either control or MCT groups (12 min). The results indicate that ADM vasodilates more rapidly in MCT and ADM pretreated rats. The effect of ADM is pronounced and long lasting in MCT- and vehicle-treated rats. It may be explained by the regulated clearance of ADM and related receptors. J Clin Basic Cardiol 2001; 4: 79-82.