To further investigate the potential pathogenetic role of the gastrointestinal microbiota in metabolic diseases such as diabetes mellitus in cats. The permanent elevation of arterial pressure during the chronic administration of low-dose exogenous ouabain strongly supports the notion that endogenous ouabain plays a major pathophysiological role in essential hypertension. If ouabain is indeed a causative agent in essential hypertension, its application to normotensive animals in pathophysiologically relevant amounts should unequivocally elevate arterial pressure. However, an increase in arterial pressure in response to the chronic application of exogenous ouabain has not always been reported. At least nine independent studies of appropriate duration and adequate ouabain dosing have not detected any arterial blood pressure elevation. Even authors that have repeatedly documented ouabain-induced hypertension have noted in some reports that the arterial blood pressure response to exogenous ouabain was variable, i.e., ouabain was causing hypertension in some rats but not in others. Nevertheless, these negative reports have mostly been ignored, and the prevailing opinion is that endogenous ouabain is an important factor in the pathogenesis of hypertension. Despite rather compelling evidence at the cellular and molecular levels that supports the postulated causal relationship between elevated ouabain and elevated arterial blood pressure, the fact that exogenous ouabain causes hypertension has not yet been proven. For instance, arterial pressure elevation associated with chronic low-dose ouabain has not been confirmed with telemetric monitoring, the recommended gold-standard method for blood pressure measurement in animals. Thus, it is possible that the reported discrepancies in arterial blood pressure response to chronic low-dose ouabain could be related to limitations associated with the tail-cuff measurements of blood pressure. Moreover, the absence of a hypotensive effect of the ouabain antagonist rostafuroxin in an OASIS-HT trial does not support a major pathophysiological role for endogenous ouabain in essential hypertension. The main goal of this study was to use radiotelemetric blood pressure monitoring to test whether the chronic administration of low-dose exogenous ouabain causes hypertension. Furthermore, we examined ouabain-induced changes in autonomic nervous system activity, the stress response, and the expression of genes that have been postulated to be critically involved in ouabaindependent hypertension. Because ouabain plasma levels are particularly elevated in patients with salt-sensitive hypertension, we explored whether the application of ouabain is associated with increased sensitivity of blood pressure to salt. Although we carefully designed our experimental protocol to mimic published research JTP-74057 showing a hypertensive effect of exogenous ouabain, we were unable to confirm this finding. We hypothesized that increased secretion of some vasodilators could prevent the hypertensive effect of ouabain and found that the plasma level of calcitonin gene-related peptide was elevated in ouabain-treated rats. The discovery of endogenous cardiotonic steroids revived interest in a half-century-old hypothesis that postulated.