Abstract

The present study demonstrates the reactivity of isolated main pulmonary artery (MPA) from guinea pigs and rats to two vasoactive drugs, norepinephrine (NE) and histamine (H), in substrate-rich and substrate-free medium, under both aerobic (PO2 = 95 +/- 0.5 Torr) and hypoxic conditions (PO2 = 30 +/- 1 Torr). The sensitivity of MPA from guinea pigs to NE and H during aerobic conditions is not significantly affected by the absence of substrate in the experimental medium. Furthermore, it is demonstrated that in the substrate-rich experimental medium (5.5 mM glucose), the reactivity of MPA from guinea pigs to NE and H is not significantly affected by acute hypoxia as compared with the response of MPA during aerobic conditions. These experiments contrast with data obtained when substrate is absent from the experimental medium. The dose-response curves of MPA from guinea pigs to NE and H under this condition were significantly blunted during hypoxia. Following the completion of the dose-response curves during aerobic conditions, with both NE and H, spontaneous mechanical activities were seen in the guinea pig MPA. On the other hand, it was demonstrated that during aerobic and hypoxic conditions MPA's isolated from rats exhibit no physiological response to histamine even when administered in the dose required to produce the maximal response in MPA isolated from guinea pigs. The sensitivity of MPA from rats to NE during aerobic conditions is not significantly affected by the absence of substrate in the experimental medium. However, when the preparation was exposed to hypoxia, the presence of substrate failed to maintain the reactivity of MPA to norepinephrine. In addition, MPA isolated from rats demonstrated a smaller contractile response to NE than those from guinea pigs. Furthermore, no spontaneous mechanical activities were observed after norepinephrine or histamine administration. The present study, in addition to pointing out species differences, shows the important role of exogenous substrate in maintaining the reactivity of pulmonary vascular smooth muscle during hypoxia.

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