Reduced Cardiovascular Reactivity to Stress but Not Feeding in Renin Enhancer Knockout Mice

Abstract

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 α-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. © 2007 American Journal of Hypertension, Ltd.