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Physiological and Molecular Mechanisms Implicated in the Neural Control of Circulation

Persistence of circadian variation in arterial blood pressure in β1/β2-adrenergic receptor-deficient mice

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

Submitted 31 January 2008 ; accepted in final form 26 February 2008

The β-adrenergic pathway has been considered one important effector of circadian variation in arterial pressure. Experiments were performed in β1/β2-adrenergic receptor-deficient mice (β1/β2ADR–/–) to assess whether this pathway is required for circadian variation in mean arterial pressure (MAP) and to determine the impact of its loss on the response to changes in dietary salt. Twenty-four-hour recordings of MAP, heart rate (HR), and locomotor activity were made in conscious 16- to 17-wk-old mice [wild-type, (WT), n = 7; β1/β2ADR–/–, n = 10] by telemetry. Both WT and β1/β2ADR–/– mice demonstrated robust circadian variation in MAP and HR, although 24-h mean MAP was 10% lower (102.02 ± 1.81 vs. 92.11 ± 2.62 mmHg) in β1/β2ADR–/– than WT, HR was 16% lower and day-night differences reduced. Both WT and β1/β2ADR–/– mice adapted to changed salt intake without changed MAP. However, the β1/β2ADR–/– mice demonstrated a striking reduction in locomotor activity in light and dark phases of the day. In WT mice, MAP was markedly affected by locomotor activity, resulting in bimodal distributions in both light and dark. When MAP was analyzed using only intervals without locomotor activity, bimodality and circadian differences were reduced, and there was no significant difference between the two genotypes. The results indicate that there is no direct effect or role for the β-adrenergic system in circadian variation of arterial pressure in mice, aside from the indirect consequences of altered locomotor activity. Our results also confirm that locomotor activity contributes strongly to circadian variation in blood pressure in mice.

salt intake; sympathetic nervous system