Cardiac function is highly dependent on oxidative energy, which is produced by mitochondrial respiration. Defects in mitochondrial function are associated with both structural and functional abnormalities in the heart. Here, we show that heart-specific ablation of the circadian clock gene Bmal1 results in cardiac mitochondrial defects that include morphological changes and functional abnormalities, such as reduced enzymatic activities within the respiratory complex. Mice without cardiac Bmal1 function show a significant decrease in the expression of genes associated with the fatty acid oxidative pathway, the tricarboxylic acid cycle, and the mitochondrial respiratory chain in the heart and develop severe progressive heart failure with age. Importantly, similar changes in gene expression related to mitochondrial oxidative metabolism are also observed in C57BL/6J mice subjected to chronic reversal of the light-dark cycle; thus, they show disrupted circadian rhythmicity. These findings indicate that the circadian clock system plays an important role in regulating mitochondrial metabolism and thereby maintains cardiac function.

Together, these data demonstrate that extracellular calcium, possibly acting through the endogenous CaR, antagonizes forskolin-induced AQP2 translocation to the apical plasma membrane in CD8 cells. In hypercalciuria, this mechanism might blunt water reabsorption and prevent further calcium concentration, thus protecting against a potential risk of urinary calcium-containing stone formation.

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Inflammation within the brainstem microvasculature has been associated with chronic cardiovascular diseases. We found that the expression of several enzymes involved in arachidonic acid (AA) - leukotriene B4 (LTB4) production was altered in NTS of SHR. LTB4 produced from AA by 5-lipoxygenase (5LOX) is a potent chemoattractant of leukocytes. Leukotriene B4-12-hydroxydehydrogenase (LTB4-12-HD), which degrades leukotriene B4 (LTB4), was down-regulated compared to Wistar-Kyoto rats (WKY). Quantitative RT-PCR revealed that LTB4-12-HD was reduced by 63 and 58% in the NTS of adult SHR and pre-hypertensive (PH) SHR respectively, compared to age-matched WKY rats (n=6). 5LOX gene expression was up-regulated in the NTS of SHR (~50%; n=6). LTB4 levels were increased in the NTS of the SHR (17%; n=10, p<0.05). LTB4 receptors BLT1 (but not BLT2), were expressed on astroglia in the NTS but not neurons or vessels. Microinjection of LTB4 into the NTS of WKY rats increased both leukocyte adherence and arterial pressure for over 4 days (peak: +15 mmHg; P<0.01). In contrast, blockade of NTS BLT1 receptors lowered blood pressure in the SHR (peak: -13 mmHg; P<0.05) but not WKY rats. Thus, excessive amounts of LTB4 in NTS of SHR possibly as a result of up-regulation of 5LOX and down regulation of LTB412-HD, can induce inflammation. Since blockade of NTS BLT1 receptors lowered arterial pressure in the SHR their endogenous activity may contribute to the hypertensive state of this rodent model. Thus, inflammatory reactions in the brainstem are causally associated with neurogenic hypertension.