Nitric oxide contributes to substance P-induced increases in lung rapidly adapting receptor activity in guinea-pigs

Abstract

1. Substance P induces fluid flux via nitric oxide, and fluid flux stimulates lung rapidly adapting receptors (RARs). We therefore proposed that nitric oxide contributes to substance P-evoked increases in RAR activity. Since substance P decreases dynamic compliance (C(dyn)), which can stimulate RARs, we also determined whether nitric oxide contributed to substance P-induced effects on pulmonary function. 2. In anaesthetized guinea-pigs, the effects of substance P on RAR activity, C(dyn), pulmonary resistance (R(L)), and arterial blood pressure were measured before and after I.V. infusion of N(G)-methyl-L-arginine (L-NMMA; a nitric oxide synthase inhibitor), or L-NMMA followd by L-arginine (a nitric oxide precursor which reverses the effects of L-NMMA). 3. Substance P-evoked increases in RAR activity were blunted by L-NMMA (P = 0.006) but not by L-NMMA-L-arginine (P = 0 42). 4. Substance P-evoked decreases in C(dyn) were slightly inhibited by L-NMMA (P = 0.02) and slightly enhanced by L-NMMA-L-arginine (P = 0.004). However, at the time at which L-NMMA maximally reduced substance P-induced RAR stimulation (the first 30 s), it did not change substance P-induced decreases in C(dyn). 5. Substance P-evoked increases in R(L) were not changed by L-NMMA (P = 0.10) and were enhanced by L-NMMA-L-arginine (P = 0 03). 6. L-NMMA-evoked increases in mean arterial blood pressure were reversed by L-arginine. Substance P-evoked decreases in mean arterial blood pressure were not changed by L-NMMA or by L-NMMA-L-arginine. 7. We conclude that nitric oxide contributes to substance P-evoked increases in RAR activity and that the increases are most probably independent of decreases in C(dyn).