Submitted on August 22, 2003
Accepted on November 11, 2004
Central Angiotensin II AT1 Receptors Mediate Fetal Swallowing and Pressor Responses in the Near Term Ovine Fetus
Mostafa A El-Haddad1*, Yaser Ismail1, Dave Gayle1, and Michael G Ross1
1 Harbor-UCLA Medical Center, David Geffen UCLA Medical School, Research and Educational Institute, Torrance, CA, USA
* To whom correspondence should be addressed. E-mail: mostafa.elhaddad{at}cox.net.
Swallowed volumes in the fetus are greater than adult values (per body weight) and serve to regulate amniotic fluid volume. Central AngII stimulates swallowing, and nonspecific AngII receptor antagonists inhibit both spontaneous and AngII-stimulated swallowing. In the adult rat, AT1 receptors mediate both stimulated drinking and pressor activities, while the role of AT2 receptors is controversial. As fetal brain contains increased AngII receptors compared to the adult brain, we sought to investigate the role of both AT1 and AT2 receptors in mediating fetal swallowing and pressor activities. Five pregnant ewes with singleton fetuses (130±1 d) were
prepared with fetal vascular and lateral ventricle (LV) catheters, electrocorticogram and esophageal electromyogram electrodes and received 3 studies over 5 days. On day 1 (AngII), following a 2 h basal period, 1 ml artificial cerebrospinal fluid (aCSF) was injected in the LV. At
time 4hr, AngII (6.4µg) was injected in the LV and the fetus monitored for a final 2h. On day 3, AT1 receptor blocker (Losartan 0.5 mg) was administered at 2h, and AngII plus losartan administered at 4h. On day 5, AT2 receptor blocker (PD-123319 0.8mg) was administered at 2h, and AngII plus PD-123319 at 4h. In the AngII study, LV injection of AngII significantly increased fetal swallowing (0.9±0.1 to 1.4±0.1 swallows/min; P<0.05). In the losartan study, basal fetal swallowing significantly decreased in response to blockade of AT1 receptors (0.9±0.1 to 0.4±0.1 swallows/min; P<0.05), while central injection of AngII in the presence of AT1 receptor antagonism did not increase fetal swallowing (0.6±0.1 swallows/min). In the PD-123319 study, basal fetal swallowing did not change in response to blockade of AT2 receptor (0.9±0.1 swallows/min), while central injection of AngII in the presence of AT2 blockade significantly increased fetal swallowing (1.5±0.1 swallows/min; P<0.05). AngII caused significant pressor
responses in the control and PD-123319 studies, but no pressor response in the presence of AT1 blockade. These data demonstrate that in the near term ovine fetus, AT1 receptor, though not AT2 receptors accessible via CSF contribute to dipsogenic and pressor responses.
