Nitric oxide mediates feedback inhibition in angiotensin II-induced upregulation of vasopressin mRNA.
Angiotensin II (Ang II) stimulates hypothalamic magnocellular neurons to release arginine vasopressin (AVP) via Ang II type 1 (AT1) receptors during chronic hyperosmotic condition. On the other hand, endogenous nitric oxide (NO) tonically inhibits the activity of AVP producing neurons; and system infusion of Ang II elicits the activity of NO producing neurons in the hypothalamus. These studies suggest that NO may mediate feedback inhibition in Ang II modulation of AVP neuronal excitability. To confirm this hypothesis, we first investigated colocalization of neuronal NO synthase (nNOS) and AT1 receptors in the hypothalamic magnocellular nuclei of adult male rats by using double immunofluorescence. We found that 60% and 65% of AT1 receptors immunoreactive neurons coexpressed nNOS in the hypothalamic paraventricular nucleus and supraoptic nucleus, respectively. We then demonstrated that intracerebroventricular administration of nNOS inhibitor N-omega-nitro-l-arginine methyl ester further enhanced upregulation of AVP mRNA level but totally abolished upregulation of nNOS mRNA level in the paraventricular and supraoptic nuclei of anesthetized rats induced by a prior administration of Ang II. Theses morphological and pharmacological data demonstrate that NO mediates negative feedback regulation of Ang II-induced upregulation of AVP mRNA.
Department of Anatomy, Histology & Embryology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
Luqing
L
Zhang
Ming
M
Tong
Ming
M
Xiao
Lei
L
Li
Jiong
J
Ding
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics; D010286:Paraventricular Hypothalamic Nucleus / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013495:Supraoptic Nucleus / Q000201:enzymology; D015854:Up-Regulation / Q000187:drug effects*; D014667:Vasopressins / Q000235:genetics*
D017931:DNA Primers; D012333:RNA, Messenger; D014667:Vasopressins; D000804:Angiotensin II; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I