Central angiotensin I increases fetal AVP neuron activity and pressor responses.
Angiotensin (Ang) II plays a critical role in cardiovascular homeostasis and neuroendocrine regulation. Little is known about whether central angiotensin-converting enzyme (ACE) is functional in the fetal brain. We investigated cardiovascular and neuroendocrinological responses to intracerebroventricular (icv) application of Ang I in the chronically prepared near-term ovine fetus in utero and examined the action sites marked by c-fos expression in the fetal hypothalamus. ACE mRNA was detected in the specific central areas. Intracerebroventricular Ang I significantly increased fetal blood pressure and c-fos expression in the supraoptic nuclei (SON) and the paraventricular nuclei (PVN) in the hypothalamus, accompanied by an increase of fetal plasma arginine vasopressin (AVP). Double labeling demonstrated that AVP neurons in the fetal SON and PVN were expressing c-fos. Captopril, an inhibitor of ACE, significantly suppressed fetal pressor responses and plasma AVP. Double labeling experiments showed colocalization of AT(1) receptor (AT(1)R) and c-fos expression in both SON and PVN following icv Ang I. The results indicate that central endogenous ACE has been functional at least at the last third of gestation and the endogenous brain renin-angiotensin system-mediated pressor responses and AVP release via AT(1)Rs by acting at the sites consistent with the cardiovascular network in the hypothalamus.
Shi
Lijun
L
Beijing Sport University and First Hospital of Soochow University, Beijing, Suzhou, China.
Mao
Caiping
C
Zeng
Fanxing
F
Hou
Jianquan
J
Zhang
Hong
H
Xu
Zhice
Z
D000803:Angiotensin I / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000502:physiology*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D005260:Female; D005333:Fetus; D006339:Heart Rate / Q000502:physiology; D006651:Histocytochemistry; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000502:physiology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D013495:Supraoptic Nucleus / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D000803:Angiotensin I; D002216:Captopril; D007703:Peptidyl-Dipeptidase A