Nitric oxide modulates angiotensin II-induced drinking behavior in the near-term ovine fetus

OBJECTIVE: Human and ovine fetuses demonstrate an enhanced rate of spontane ous and angiotensin II-stimulated swallowing. Angiotensin II and nitric oxi de synthase have been localized to thirst centers in the brain. This study was performed to determine whether central nitric oxide contributes to the regulation of angiotensin II-induced fetal swallowing. STUDY DESIGN: Six pregnant ewes with near-term singleton fetuses were chron ically prepared with fetal vascular and lateral ventricle catheters and ele ctrocorticogram and esophageal electromyogram electrodes. After a 2-hour co ntrol period, fetuses were administered serial lateral ventricle injections (1 mL) of angiotensin II (3.2 mu g; time, 2 hours) and N omega-nitro-L-arg inine methyl ester (3 mg; time, 3 hours) and a repeat angiotensin II inject ion (3.2 mu g; time, 5 hours). All fetuses received an additional control s tudy of lateral ventricle injections of artificial cerebrospinal fluid on a previous day. RESULTS: Angiotensin II injection significantly increased mean +/- SEM feta l swallowing (0.9 +/- 0.1 to 2.7 +/- 0.4 swallows/min). N omega-nitro-L-arg inine methyl ester significantly decreased fetal swallowing to below the ba sal rate (0.4 +/- 0.1 swallows/min), and swallowing did not increase with t he second angiotensin II dose (in the presence of nitric oxide blockade). CONCLUSIONS: These results demonstrate that inhibition of central nitric ox ide suppresses fetal swallowing behavior in response to central angiotensin II. We speculate that tonic nitric oxide facilitates angiotensin II swallo wing stimulation by maintenance of glutamate activation of hypothalamic N-m ethyl-D-aspartate receptors.