Diurnal Rhythm in Blood Pressure Is Preserved in Hypertensive Mice Despite Therapy With Mineralocorticoid Receptor Antagonists.

Abstract

Human arterial blood pressure follows a circadian rhythm, where pressure is highest during the day and lowest during the night. Patients with hypertension can have either a preserved rhythm or a dampened rhythm with a lower day-to-night difference, called "dippers" and "nondippers," respectively. Spironolactone, eplerenone, and the newer finerenone are mineralocorticoid receptor antagonists (MRAs) used for patients with resistant hypertension. In this study, we describe the 24h diurnal cycle in blood pressure in mice with and without hypertension to test whether high blood pressure induced a nondipping phenotype. Moreover, we tested whether the 3 MRAs affected the 24h cycles in blood pressure in the mice. Radiotelemetry devices were used to monitor blood pressure continuously in freely roaming mice (n = 19). Hypertension was induced by l -nitroarginine methyl ester ( l -NAME, 1 g/L) dissolved in the drinking water. A dipping phenotype was acknowledged if the nocturnal reduction in blood pressure was >10%. The 3 MRAs were administered orally once daily. Significant 24h rhythms were identified in blood pressure and 89% of the mice had a dipping phenotype at baseline. Only 42% of the hypertensive mice were dippers ( P > 0.05 vs. baseline). The MRAs at the doses tested did not change the 24h rhythm in blood pressure, and they did not restore a dipping phenotype in the nondipping hypertensive mice. Thus, l -NAME causes hypertension in mice and induces a "nondipper" phenotype in most of the mice. Spironolactone, eplerenone, or finerenone at the selected doses do not change arterial blood pressure in hypertensive mice.