title: Cardiovascular effects of overexpression of endothelial nitric oxide synthase in the rostral ventrolateral medulla in stroke-prone spontaneously hypertensive rats.
abstract: We have previously demonstrated that the overexpression of endothelial NO synthase (eNOS) in the rostral ventrolateral medulla (RVLM) decreases blood pressure, heart rate, and sympathetic nerve activity via an increase in gamma-amino butyric acid release in normotensive Wistar-Kyoto rats (WKY). Stroke-prone spontaneously hypertensive rats (SHRSP) appear to have reductions of NO production and GABA release in the RVLM. The aim of this study was to determine whether the effects of the increase in NO production in the RVLM in SHRSP are different from those in WKY. We transfected adenovirus vectors encoding either eNOS (AdeNOS) or beta-galactosidase (Adbetagal) into the RVLM of both strains. In the AdeNOS-treated group, mean arterial blood pressure and heart rate in the conscious state were significantly decreased at day 7 after the gene transfer in both strains. The decreases in mean arterial blood pressure and heart rate were significantly greater in SHRSP than in WKY. Urinary norepinephrine excretion was also decreased to a greater degree in SHRSP than in WKY after the gene transfer. The pressor response evoked by bicuculline into the RVLM of WKY was greater than that of SHRSP in the nontransfected group. However, in the AdeNOS-treated group, the pressor response did not differ between SHRSP and WKY after the gene transfer. These results indicate that the increase in NO production evoked by the overexpression of eNOS in the RVLM causes greater depressor and sympathoinhibitory responses in SHRSP than in WKY by improving an inhibitory action of GABA on the RVLM neurons.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Koji
authors.initials: K
authors.lastname: Ito
authors.forename: Koji
authors.initials: K
authors.lastname: Sakai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology* / Q000652:urine; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D001616:beta-Galactosidase; D001640:Bicuculline