Enhanced depressor response to endothelial nitric oxide synthase gene transfer into the nucleus tractus solitarii of spontaneously hypertensive rats.
Previously, we demonstrated that endothelial nitric oxide synthase (eNOS) gene transfer into the nucleus tractus solitarii (NTS) decreased blood pressure, heart rate and sympathetic nerve activity in conscious normotensive Wistar-Kyoto rats (WKY). In order to determine whether overexpression of eNOS in the NTS causes different effects on blood pressure and heart rate between spontaneously hypertensive rats (SHR) and WKY, we transfected adenovirus vectors encoding either eNOS (AdeNOS) or beta-galactosidase (Ad beta gal) into the NTS of SHR and WKY in vivo. The local expression of eNOS in the NTS was confirmed by Western blot analysis for eNOS protein, and the magnitude of expression did not differ between SHR and WKY. Blood pressure and heart rate were monitored by the use of a radio-telemetry system in a conscious state before and 7 days after the gene transfer. Systolic blood pressure (SBP) and heart rate decreased on day 7 in both AdeNOS-transfected SHR and WKY. However, the magnitude of decreases in SBP of AdeNOS-transfected SHR was greater than that of AdeNOS-transfected WKY (-24.1 +/- 2.9 vs. -15.9 +/- 2.1 mmHg, p < 0.05). Transfection of Ad beta gal into the NTS did not alter SBP in either group. A depressor response evoked by microinjection of L-glutamate into the NTS did not differ between the two strains. These results suggest that overexpression of eNOS in the NTS causes a greater depressor response in SHR than in WKY in a conscious state. An abnormality of the L-arginine-NO pathway in the NTS may be related to the hypertensive mechanism(s) of SHR.
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. hyoshi@cardiol.med.kyushu-u.ac.jp
Yoshitaka
Y
Hirooka
Koji
K
Sakai
Takuya
T
Kishi
Koji
K
Ito
Hiroaki
H
Shimokawa
Akira
A
Takeshita
D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D002946:Cisterna Magna; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D018698:Glutamic Acid / Q000008:administration & dosage / Q000494:pharmacology; D006339:Heart Rate / Q000235:genetics; D006973:Hypertension / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008845:Microinjections; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D009638:Norepinephrine / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017552:Solitary Nucleus / Q000201:enzymology*; D013686:Telemetry; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D001616:beta-Galactosidase; D009638:Norepinephrine