Effect of no synthase inhibition on cerebral blood flow responses to co; in fetal sheep

Inhibition of NO synthase in mature brain reduces the cerebral blood flow (CBF) response to CO, in some species. We tested whether inhibition by Nnitro-L-arginine (L-NAME; 60 mg/kg, iv) in midgestation (93 days; n=6) and near-term (133 days; n=7) fetal sheep reduces CO2 responses. In chronicallycatheterized 93 day fetuses, hypercapnia (ΔPaCO₂=19mmHg) increased microsphere-determined CBF (ml/min/100g) from 45±4 to 82±6 (±SE) before L-NAME and from 33±5 to 54±7 after L-NAME. Cerebrovascular resistance (CVR; mmHg/ml/min/100g) decreased from 0.97±0.07 to 0.56±0.04 before L-NAME and from 1.64±0.20 to 0.96±0.08 after LNAME. The percent change in CBF per A mmHg PaCO, was similar before (4.6±0.7/ΔmmHg) and after (3.7±1.0) L-NAME. Likewise, CVR % reactivity was similar before (2.2±0.3%/ΔmmHg) and after (2.0±0.4) L-NAME. In 133 day fetuses hypercapnia increased CBF from 129±11 to 265±23 before L-NAME and from 94±6 to 164±14 after L-NAME. CVR decreased from 0.45±0.05 to 0.22±0.02 before L-NAME and from 0.82±0.05 to 0.46±0.05 after L-NAME. CBF % reactivity was similar before (4.0±0.7) and after (3.5±0.9) L-NAME. CVR % reactivity was also similar before (1.7±0.2) and after (2.0±0.4) L-NAME. We conclude that NO synthase inhibition decreases baseline CBF and increases baseline CVR as early as 93 days in fetal sheep, indicating a tonic effect of NO by midgestation. However, NO synthase inhibition does not impede CO₂ reactivity at midgestation or near term. (Supported by NS20020).