THE INTERACTION OF ALPHA-HUMAN ATRIAL-NATRIURETIC-PEPTIDE (ANP) WITH SALBUTAMOL, SODIUM-NITROPRUSSIDE AND ISOSORBIDE DINITRATE IN HUMAN BRONCHIAL SMOOTH-MUSCLE

1 Contractions in human bronchial rings evoked by methacholine (10(-6) M) were reversed by single contractions of a-human atrial natriuretic peptide (10(-6) M), salbutamol (10(-6) M), sodium nitroprusside (10(- 6) M) or isosorbide dinitrate (4.2 x 10(-5) M) and the extent of the r elaxations compared. The activity of combinations of ANP with salbutam ol, sodium nitroprusside and isosorbide dinitrate were compared with t hose for each agonist alone. 2 ANP and salbutamol were equipotent in r eversing methacholine-evoked contraction and, in combination these ago nists evoked an additive response. ANP and sodium nitroprusside also e voked similar degrees of relaxation and were additive, as were ANP and isosorbide dinitrate; however, with isosorbide dinitrate a higher con centration was required to evoke the same degree of relaxation as ANP, sodium nitroprusside or salbutamol. 3 Cumulative concentration-respon se curves to methacholine (10(-9)-3 x 10(-4) M) were examined in the p resence and absence of the above bronchodilator substances, alone and in combination allowing their abilities to protect against contraction to be compared. ANP (10(-6) M) and salbutamol (10(-6) M) each attenua ted subsequent contractions evoked by methacholine, an ability not sha red with sodium nitroprusside (10(-6) M) or isosorbide dinitrate (4.2 x 10(-5) M). Indeed at lower concentrations of methacholine (<3 x 10(- 7) M), sodium nitroprusside evoked a paradoxical enhancement of methac holine-evoked contractions. 4 In combination, ANP and salbutamol atten uated contractions evoked by methacholine to a significantly greater d egree than that seen with either agonist alone, whilst a combination o f ANP and sodium nitroprusside evoked no greater effect than that seen with ANP alone. By contrast, isosorbide dinitrate and ANP together ev oked a greater inhibition than ANP alone. 5 These results suggest that a combination of agents such as ANP and salbutamol evokes a greater e ffect than either alone, both in reversing and protecting against meth acholine-evoked contractions. Such combinations may be of benefit in t he treatment of patients, allowing lower doses of drug to be used. Com binations of ANP and isosorbide dinitrate may likewise be of interest; however, the mechanism underlying the enhancement of ANP responses by isosorbide dinitrate requires further study.