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REGULATION IN GENETICALLY MODIFIED ANIMALS

Dbh(-/-) mice are hypotensive, have altered circadian rhythms, and have abnormal responses to dieting and stress

¹Department of Biology, Williams College, Williamstown, Massachusetts 01267; and ²Howard Hughes Medical Institute and Department of Biochemistry, University of Washington, Seattle, Washington 95195

Submitted 21 July 2003 ; accepted in final form 10 September 2003

We used mice deficient in dopamine -hydroxylase [Dbh(-/-)] and their littermate controls [Dbh(+/-)] to examine the role of epinephrine (Epi) and norepinephrine (NE) in the maintenance of cardiovascular parameters during 7 days of caloric restriction and acute exposure to environmental stress. Cardiovascular parameters of the mice were monitored using blood pressure radiotelemeters at an ambient temperature of 29°C. Under normal conditions, Dbh(-/-) mice had a low heart rate, were severely hypotensive, and displayed an attenuated circadian blood pressure rhythm. Upon 50% caloric restriction, Dbh(+/-) mice exhibited decreases in heart rate and mean blood pressure. However, the blood pressures of Dbh(-/-) mice did not fall significantly in response to caloric restriction, and the bradycardia associated with caloric restriction was attenuated in these mice. In response to an open-field test, the blood pressure and heart rate of Dbh(+/-) mice increased substantially and rapidly, whereas Dbh(-/-) mice had blunted changes in blood pressures and no change in heart rate. These data suggest a primary role of Epi and NE in mediating the hypotension induced by dieting. Furthermore, Epi and NE play a smaller, but still significant, role in the bradycardia induced by caloric restriction. In contrast, Epi and NE are required for the tachycardia in an open field but are not required for the increase in blood pressure.

hypertension; blood pressure; food restriction; sympathetic nervous system; radiotelemetry; dopamine -hydroxylase-deficient mice

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