Diurnal rhythm in blood pressure is preserved in hypertensive mice despite therapy with mineralocorticoid receptor antagonists

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 "non-dippers", respectively. Spironolactone, eplerenone and the newer finerenone are mineralocorticoid receptor antagonists (MRAs) used for patients with resistant hypertension. In the present study, we describe the 24h diurnal cycle in blood pressure in mice with and without hypertension to test if high blood pressure induced a non-dipping phenotype. Moreover, we tested if the three 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 versus 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 non-dipping hypertensive mice. Thus, L-NAME causes hypertension in mice and induces a "non-dipper" phenotype in most of the mice. Spironolactone, eplerenone or finerenone at the selected doses do not change arterial blood pressure in hypertensive mice.