1. We have examined the possibility that daily blood pressure rhythms are produced by variations in the production of prostanoids. Comparing circadian blood pressure and heart rate rhythms in wild type and COX2-/- deficient mice by radiotelemetry we found that absence of COX2 did not alter the robust cardiovascular rhythmicity observed in wild type mice. 24 hour mean arterial blood pressure tended to be higher in COX-2-/- than WT mice (127 plus/minus 4 vs. 119 plus/minus 3 mm Hg; p=0.136). Plasma volume was not different between WT and COX-2-/- mice. Mean arterial blood pressure was not significantly altered by either low or high Na diets in WT mice (114 plus/minus 4 mm Hg at low Na, and 114 plus/minus 2 mm Hg at high Na). In COX-2-/- mice, the low Na diet did not significantly alter blood pressure (130 plus/minus 7 mm Hg) whereas a high Na diet elevated blood pressure by about 10 mm Hg (142 plus/minus 5 mm Hg) in the night time. Glomerular filtration rate was lower in COX-2-/- mice regardless of genetic background. Thus, whereas the expression of COX2 modifies the blood pressure response to salt intake, it does not seem to play a major role in the generation of circadian blood pressure or heart rate rhythms.? ? 2. The most widely used method to assess circadian rhythms is to determine the locomotor activity using running wheels and counting of wheel revolutions as measure of activity. We have developed this method as a complementary approach to determinations of blood pressure and heart rate rhythms. Wheel running activity is examined in cages equipped with stainless steel running wheels (Mini-Mitter, Oregon). Since photic input is a strong determinant of rhythmicity the lighting conditions have to be considered. When located in the animal room running activity can be assessed under conditions of a 12h light/12 h dark lighting cycle. In order to assess true endogenous rhythms independent of light cues, experiments have to be performed under conditions of 24 hour darkness. We have set up housing conditions permitting light control independent of the room lighting by using a ventilated box with its own light controls. Running wheel revolutions are quantified by a magnetic reed switch next to the wheel, and data are stored on a PC using Vital View software (Mini-Mitter, Oregon). We are currently collecting data from an 8 day period and analyze these data with Matlab software (The Mathworks, Inc. ME) and the Clocklab Toolbox (Actimetrics, IL). We have used this approach to further examine the locomotor behavior of NKCC1-deficient mice using 3 female WT and 3 female mutant animals. We found that wheel running activity is dramatically depressed in NKCC1-/- mice. Furthermore, depiction of running data in double-plotted actograms indicates that wheel running activity in NKCC1-/- mice showed either absence of significant periodicity or a greatly reduced period strength as indicated by the low Qp values whereas running in WT mice occurred in a robust circadian fashion with a period length of about 24 h as dictated by the light cycle. These data are unexpected since the shaker-waltzer behavior of circling and head bobbing characteristic for inner ear abnormalities creates the impression of hyperactivity in NKCC1-/- mice. We are currently developing a method of tracking mouse movements using a camera and computer-assisted motion analysis.
| Kim, Soo Mi; Theilig, Franziska; Qin, Yan et al. (2009) Dense-core vesicle proteins IA-2 and IA-2{beta} affect renin synthesis and secretion through the {beta}-adrenergic pathway. Am J Physiol Renal Physiol 296:F382-9 |
| Kim, Soo Mi; Chen, Limeng; Faulhaber-Walter, Robert et al. (2007) Regulation of renin secretion and expression in mice deficient in beta1- and beta2-adrenergic receptors. Hypertension 50:103-9 |
