title: Gene transfer of angiotensin-converting enzyme 2 in the nucleus tractus solitarius improves baroreceptor heart rate reflex in spontaneously hypertensive rats.
abstract: The renin-angiotensin system (RAS) in the nucleus tractus solitarius (NTS) is an important modulator of the baroreceptor heart rate reflex. This study tested the hypothesis that angiotensin-converting enzyme 2 (ACE2) expression is decreased in the NTS of spontaneously hypertensive rats (SHRs) and that its gene transfer in this nucleus would lead to beneficial effects on baroreflex function since this enzyme is key in the regulation of the vasoprotective axis of the RAS. ACE2 protein levels and its activity were significantly decreased in the NTS of SHRs compared to normotensive Wistar-Kyoto (WKY) control rats. Rats instrumented with radio-telemetry transducers received NTS microinjection of either Lenti-ACE2 (Lentiviral vector-mediated gene transfer of ACE2) or lenti-GFP (green fluorescent protein). The ACE2 gene transfer into the NTS resulted in long-term overexpression of ACE2. This was associated with a 60% increase in heart rate baroreflex sensitivity in the lenti-ACE2 injected SHRs compared with the lenti-GFP injected control SHRs (0.27 ± 0.02 ms/mmHg in lenti-GFP rats vs. 0.44 ± 0.07 ms/mmHg in lenti-ACE2 rats). These observations demonstrate that ACE2 gene transfer overcomes its intrinsic decrease in the NTS of SHRs and improves baroreceptor heart rate reflex.
authors: Department of Physiology and Functional Genomics, College of Medicine and McKnight Brain Institute, University of Florida, Gainesville, FL, USA. mayamaz-ryk@umin.ac.jp
authors: Masanobu
authors: M
authors: Yamazato
authors: Anderson J
authors: AJ
authors: Ferreira
authors: Yoriko
authors: Y
authors: Yamazato
authors: Carlos
authors: C
authors: Diez-Freire
authors: Lihui
authors: L
authors: Yuan
authors: Robert
authors: R
authors: Gillies
authors: Mohan K
authors: MK
authors: Raizada
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D018014:Gene Transfer Techniques; D006339:Heart Rate / Q000502:physiology*; D016086:Lentivirus / Q000235:genetics; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017552:Solitary Nucleus / Q000378:metabolism* / Q000503:physiopathology; D014161:Transduction, Genetic
chemical_list: D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2