Baroreflex responses in neuronal nitric oxide synthase knoukout mice (nNOS).
The present study sought to determine the influence of the neuronal isoform of nitric oxide synthase (nNOS) on the baroreflex gain (mean index: bpm/mm Hg) and on the respiratory response to baroreflex activation by using nNOS knockout (nNOS-/-) mice. Experiments were performed with nNOS+/+ wild type (WT; n=12) and nNOS-/- mice (n=11), both of the C57Bl6 strain, randomly assigned to the two groups. Carotid artery and external jugular vein were cannulated under halothane, and after recuperation, urethane was intravenously injected. Baroreflex gain was evaluated by intravenous injection of phenylephrine (PE: 15-18 microg/kg) and sodium nitroprusside (SNP: 46-50 microg/kg) in WT and nNOS-/- anesthetized mice. At baseline, nNOS-/- mice had a comparable heart rate (604.5+/-23.6 vs. 618.7+/-11.2 bpm) but higher mean arterial pressure (112.4+/-6.3 vs. 94.8+/-3.9 mm Hg, P<0.05) than WT mice. Heart rate reflex was significantly reduced (P<0.05) in nNOS-/- mice, tachycardic and bradycardic responses were -1.04+/-0.3 and -2.03+/-0.5 in nNOS-/- mice vs. -4+/-0.7 and -4.52+/-0.2 in WT mice, respectively. To characterize the effect of arterial pressure changes on respiratory output, PE was injected in a separate group of WT (n=7) and nNOS-/- (n=6) mice. Tidal diaphragm activity decreased in WT mice (P<0.05); however, diaphragm minute respiration and respiratory frequency were not different between the strains of mice. In nNOS-/- group, heart rate reflex by PE injection was significantly reduced (P<0.05). These findings suggest that the absence of nNOS activity leads to an elevation of the baseline blood pressure and also shows the importance of this enzyme on the transmission of baroreflex signals.
Carvalho
Tais H F
TH
taishfc@fcr.epm.br
Lopes
Oswaldo U
OU
Tolentino-Silva
Fatima R
FR
D000704:Analysis of Variance; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000235:genetics*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D052248:Nitric Oxide Synthase Type I / Q000172:deficiency*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D052248:Nitric Oxide Synthase Type I