EFFECTS OF GROUP-B STREPTOCOCCUS ON THE RESPONSES TO U46619, ENDOTHELIN-1, AND NORADRENALINE IN ISOLATED PULMONARY AND MESENTERIC-ARTERIES OF PIGLETS

The release of endogenous vasoconstrictors together with changes in th e vascular responses are central to the pathophysiology of sepsis. The effects of in vitro incubation for 20 h with heat-killed group B Stre ptococcus (GBS, 3 X 10(7) colony-forming units mL(-1)) on the vasocons trictor responses to noradrenaline (NA, 10(-8) to 10(-4) M), the throm boxane A(2) analog 9,11-dideoxy-11 alpha,9 alpha-epoxymethanoprostagla ndin F-2 alpha (U46619; 10(-10) M to 10(-6) M) and endothelin-1 (ET-1, 10(-11) to 3 X 10(-9) M) were evaluated on isolated intrapulmonary an d mesenteric arteries from 10-17-d-old piglets. The incubation with GB S reduced the maximal contractile response to NA and ET-1 (p < 0.01) i n both arteries. The nitric oxide (NO) synthase (NOS) inhibitor N-omeg a-nitro-L-arginine methyl ester (L-NAME; 10(-4) M) completely reversed this hyporesponsiveness. GBS-treated mesenteric arteries also showed a significant reduction of the maximal contractions induced by U46619 (p < 0.05) and this effect was inhibited by 10(-4) M L-NAME. In contra st, the maximal contractile responses to U46619 were similar in contro l and in GBS-treated pulmonary arteries. Addition of L-NAME did not mo dify the contractile responses to U46619 in GBS-treated pulmonary arte ries. In conclusion, GBS-treated systemic arteries from neonatal pigle ts showed decreased responses to NA, U46619, and ET-1 due to enhanced NO release. GBS-treated pulmonary arteries also exhibited decreased re sponses to NA and ET-1 but not to U46619. Induction of NOS in vascular smooth muscle may play a key role in the hypotension and loss of syst emic vascular responsiveness that occurs in GBS sepsis. The absence of pulmonary hyporesponsiveness to U46619 may partially explain the coex istence during sepsis of pulmonary hypertension and lung NOS induction .