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Genetic and pharmacological dissection of pathways involved in the angiotensin II‐mediated depression of baroreflex function
Author(s) -
Wong LiangFong,
Polson Jaimie W.,
Murphy David,
Paton Julian F. R.,
Kasparov Sergey
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0099com
Subject(s) - baroreflex , angiotensin ii , endocrinology , medicine , rostral ventrolateral medulla , enos , calcium in biology , phospholipase c , chemistry , angiotensin ii receptor type 1 , solitary tract , nitric oxide synthase , nitric oxide , receptor , medulla oblongata , central nervous system , heart rate , blood pressure
Heart failure and hypertension are associated with increases in angiotensin II (ANG II) activity. One brain area where ANG II effects may be particularly important in these situations is the nucleus of the solitary tract (NTS). Located in the dorsomedial medulla, the NTS is the termination site of baroreceptor afferents and is essential for mediating the baroreflex. In hypertensive animals the baroreflex is impaired; this may be reversed by antagonizing ANG II AT 1 receptors in the NTS. Recently, we showed that the baroreflex depressant action of ANG II in the NTS is mediated by activation of endothelial nitric oxide synthase (eNOS) and enhanced release of GABA. Using conventional pharmacological tools and a range of adenoviral‐mediated expression of dominant negative proteins, we have determined the intracellular pathway(s) in the NTS by which ANG II activates eNOS. Our data indicate that ANG II acting in the NTS depresses the baroreflex via aG q protein‐mediated activation of phospholipase C, which through 1,4,5‐inositol triphosphate causes release of calcium from the IP3‐sensitive intracellular stores and calcium‐calmodulin formation. In contrast, multiple site disruption of a pathway leading to eNOS activation via the serine/threonine kinase Akt was ineffective.—Wong, L.‐F., Polson, J. W., Murphy, D., Paton, J. F. R., Kasparov, S. Genetic and pharmacological dissection of pathways involved in the angiotensin II‐mediated depression of baroreflex function. FASEB J . 16, 1595–1601 (2002)