Reduced baroreceptor sensitivity during hypotension in ANP-knockout mice

We studied baroreflex gain in inactin-anesthetized mice that had been genet ically modified to be depleted of atrial natriuretic peptide (ANP -/-). Wil d-type mice (ANP +/+) served as controls. ANP -/- mice had a significantly higher basal arterial blood pressure (ABP) than ANP +/+ mice [112 +/- 7 vs. 80 +/- 5 mmHg (mean +/- SEM)]. Their basal heart rates were not different (491 +/- 13 vs. 446 +/- 19 bpm). A third group, composed of ANP +/+ mice on ly, was rendered acutely hypertensive by an intravenous infusion of arginin e vasopressin acetate (0.3 pg bolus followed by 0.3 pg/h) so as to serve as a control for the elevated ABP in the ANP -/- mice. Transient changes in A BP were caused by bolus injections of oxymetazoline hydrochloride (1.5-3 ng ) or sodium nitroprusside (20-100 ng). Baroreflex gain was calculated as th e ratio of the peak heart rate change that followed the peak change in mean ABP resulting from injection of oxymetazoline or nitroprusside. There were no significant differences among the groups in their responses to transien t hypertension. On the other hand, the ANP -/- mice showed a significantly depressed tachycardic response to transient hypotension when compared with the other two groups. We conclude that the ANP -/- mice are unable to incre ase efferent sympathetic nervous activity adequately above the high basal a ctivity that is a feature of this animal model.