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This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Sabharwal, R. Articles by Chapleau, M. W PubMed Articles by Sabharwal, R. Articles by Chapleau, M. W

ApoE–/–R+A+ Mice with Hypercholesterolemia, Hypertension, and Decreased Baroreflex Sensitivity Spontaneously Develop Heart Failure with Age

¹ Univ of Iowa, 400 Hawkins Dr, Iowa City, IA, 52242,
² Vet Aff Med Ctr, Hwy 6W, Iowa City, IA, 52246

ABSTRACT

We recently created a mouse model of combined hypercholesterolemia and hypertension (HT) by inter-breeding apolipoprotein E deficient (ApoE^–/–) and renin-angiotensinogen transgenic (R⁺A⁺) mice. ApoE^–/–R⁺A⁺ and R⁺A⁺ mice had similar mean blood pressure (BP) (156±2 and 153±4 mmHg at <25 wks of age), but the ApoE^–/–R⁺A⁺ mice exhibited a much shorter lifespan (Clin Auton Res 15:2005). We hypothesized that high mortality in ApoE^–/–R⁺A⁺ mice is related to development of heart failure with age. Cardiac function (echocardiography) and BP and heart rate (HR) (telemetry) were measured in 40–60 week old female mice. Spontaneous baroreflex sensitivity (BRS) was calculated using the sequence technique. Increased lung weight confirmed heart failure. R⁺A⁺ mice had HT and decreased BRS, but normal left ventricular ejection fraction (EF) and lung weight (Table). In contrast, ApoE^–/–R⁺A⁺ mice were no longer HT at this age, but exhibited decreased BRS, decreased EF, and increased lung weight. (* vs. Control, vs. R⁺A⁺, P<0.05).

BRS was also decreased in young (<25 wks) ApoE^–/–R⁺A⁺ mice (0.97±0.2 vs. 1.90±0.3 ms/mmHg in controls) before development of heart failure. We conclude:

1. ApoE^–/–R⁺A⁺ mice are HT in early adulthood, but HT dissipates as heart failure develops with age;
   
2. BRS is decreased at a young age in this model prior to heart failure and the impairment persists in the heart failure state despite reversal of HT.
   

(VA, HL14388)

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Sabharwal, R. Articles by Chapleau, M. W PubMed Articles by Sabharwal, R. Articles by Chapleau, M. W