Reduced cardiovascular reactivity to stress but not feeding in renin enhancer knockout mice.
BACKGROUND
We have recently shown that the renin enhancer, a regulatory element of renin gene transcription, is important in the long-term control of basal blood pressure (BP). In this study, we examined whether the renin enhancer deficit alters the acute pressor response to emotional stress in mice.


METHODS
Under fluothane anesthesia, wild-type (C57BL6, n=7) and the Ren-1c enhancer knockout (REKO, n=8) mice were implanted with telemetry devices to measure BP and locomotor activity.


RESULTS
Resting BP in REKO mice (94+/-3 mm Hg) was lower than in wild-type mice (102+/-2 mm Hg). Shaker stress elicited prompt pressor (+25+/-2 mm Hg), tachycardic (+145+/-25 beats/min), and locomotor responses in wild-type mice. The BP and locomotor responses were decreased in REKO mice by 39%+/-12% (P=.03) and 64%+/-11% (P=.02), respectively, whereas the tachycardic response remained unchanged. Restraint stress increased BP by 27+/-1 mm Hg in wild-type mice. The BP response was attenuated in REKO mice by 21%+/-8% (P=.05), and this attenuation could not be ascribed to reduced locomotor activity during stress. Cardiovascular arousal associated with presentation and eating palatable food was similar in wild-type (+19+/-2 mm Hg and +174+/-21 beats/min) and REKO (+19+/-2 mm Hg and +147+/-17 beats/min) mice. The contractile response to the alpha-adrenoceptor agonist phenylephrine was reduced in aortas from REKO mice, whereas that to angiotensin II was not different between strains.


CONCLUSIONS
The disrupted regulation of renin synthesis caused by the renin enhancer deficit in mice is associated with a selective reduction in BP reactivity to aversive stress, which may be mediated by multiple central and peripheral mechanisms.
Jackson
Kristy
K
Baker Heart Research Institute, Melbourne, Victoria, Australia.
Head
Geoffrey A
GA
Morris
Brian J
BJ
Chin-Dusting
Jaye
J
Jones
Emma
E
La Greca
Luisa
L
Mayorov
Dmitry N
DN
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000821:Animal Feed; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology*; D004195:Disease Models, Animal; D006339:Heart Rate / Q000502:physiology*; D008124:Locomotion / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010656:Phenylephrine / Q000494:pharmacology; D012083:Renin / Q000097:blood*; D012149:Restraint, Physical; D012307:Risk Factors; D013315:Stress, Psychological / Q000097:blood / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D010656:Phenylephrine; D012083:Renin; D000109:Acetylcholine