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Adenoviral vector demonstrates that angiotensin II‐induced depression of the cardiac baroreflex is mediated by endothelial nitric oxide synthase in the nucleus tractus solitarii of the rat
Author(s) -
Paton Julian F. R.,
Deuchars Jim,
Ahmad Zai,
Wong L.F.,
Murphy David,
Kasparov Sergey
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0445i.x
Subject(s) - nitric oxide synthase , baroreflex , nitric oxide , nucleus , endothelial nitric oxide synthase , chemistry , angiotensin ii , medicine , pharmacology , endocrinology , anesthesia , neuroscience , biology , blood pressure , heart rate , enos
1 Angiotensin II (ANGII) acting on ANGII type 1 (AT 1 ) receptors in the solitary tract nucleus (NTS) depresses the baroreflex. Since ANGII stimulates the release of nitric oxide (NO), we tested whether the ANGII‐mediated depression of the baroreflex in the NTS depended on NO release. 2 In a working heart‐brainstem preparation (WHBP) of rat NTS microinjection of either ANGII (500 fmol) or a NO donor (diethylamine nonoate, 500 pmol) both depressed baroreflex gain by ‐56 and ‐67 %, respectively ( P < 0.01 ). In contrast, whilst ANGII potentiated the peripheral chemoreflex, the NO donor was without effect. 3 NTS microinjection of non‐selective NO synthase (NOS) inhibitors ( l ‐NAME; 50 pmol) or ( l ‐NMMA; 200 pmol) prevented the ANGII‐induced baroreflex attenuation ( P > 0.1). In contrast, a neurone‐specific NOS inhibitor, TRIM (50 pmol), was without effect. 4 Using an adenoviral vector, a dominant negative mutant of endothelial NOS (TeNOS) was expressed bilaterally in the NTS. Expression of TeNOS affected neither baseline cardiovascular parameters nor baroreflex sensitivity. However, ANGII microinjected into the transfected region failed to affect the baroreflex. 5 Immunostaining revealed that eNOS‐positive neurones were more numerous than those labelled for AT 1 receptors. Neurones double labelled for both AT 1 receptors and eNOS comprised 23 ± 5.4 % of the eNOS‐positive cells and 57 ± 9.2 % of the AT 1 receptor‐positive cells. Endothelial cells were also double labelled for eNOS and AT 1 receptors. 6 We suggest that ANGII activates eNOS located in either neurones and/or endothelial cells to release NO, which acts selectively to depress the baroreflex.