Hypoxic pulmonary vasoconstriction (HPV) is an intrapulmonary adaptive mechanism that matches alveolar ventilation to perfusion. However during prolonged alveolar hypoxia HPV occurs with many pulmonary diseases. Despite intensive studies, cellular mechanisms of HPV are still not well defined. G proteins are a family of membrane-associated proteins believed to be involved in the transduction of various signals including the regulation of vascular tonus. In this study, we aimed to determine the contribution of G(i) and G(s) proteins in hypoxic vasoconstriction of lamb isolated pulmonary artery rings. Pulmonary arteries were isolated from left lower lobe of freshly slaughtered lamb. Arteries suspended in an organ bath filled with Krebs-Henseleit solution and isometric contraction recorded continuously via an isometric transducer connected to a computerised polygraphy system. The solution aerated with 75% N-2 - 20% O-2 - 5% CO2 (normoxic) and 95% N-2 - 5% CO2 (hypoxic) pO(2) of bathing medium was measured continuosly using an oxygen electrode. Pertussis toxin and cholera toxin were used to investigate the role of G(i) and G(s) proteins. In the present study, we observed that hypoxia had no effect on resting force in large artery rings, but it caused a further contraction (1.7 +/- 0.5 mN/mm(2), n=10) in 3 mu M 5-HT precontracted pulmonary arteries rings. Hypoxic vasoconstriction was inhibited by preincubation with 2 mu g/ml cholera toxins (from 2.6 +/- 0.4 mN/mm(2), to 1.0 +/- 0.4 mN/mm(2), n=6) and potentiated by preincubation with pertussis toxins (2 mu g/ml) (from 0.6 +/- 0.4 mN/mm(2), to 1.7 +/- 0.3 mN/mm(2), n=6). These results indicate that signal transduction mediated by G(i) and G(s) proteins may be an important mechanism in the hypoxic vasoconstriction in lamb isolated large pulmonary arteries.