Circadian regulation of blood pressure: mechanisms and therapeutic implications.

An abolished or even inverse blood pressure [BP] rhythm with peak values at night is documented for most cases of human secondary hypertension, the mechanisms being unknown. Studying BP and heart rate [HR] rhythms by telemetry in normotensive and hypertensive nocturnally active rats we have shown that transgenic hypertensive rats [TGR(mRen-2)27] exhibit a dissociation between BP and HR with peak values in BP in the resting (light [L]) phase whereas HR still peaks in the activity (dark) phase, exhibiting a pattern as observed in human secondary hypertension. In comparison to Sprague-Dawley rats [SDR] from which TGR were bred, we now show that in TGR 24-h profiles in plasma renin activity are 7-fold (peak in L) and in aldosterone concentration are 3-fold higher than in SDR. Moreover, corticosterone rhythm in TGR has a greater amplitude due to exclusively higher values in L. Data indicate that these altered rhythms may contribute to the disturbed BP profile in TGR. Both the ACE-inhibitor enalapril and the AT1-receptor antagonist losartan have a greater antihypertensive efficacy in TGR after dosing in L, thereby normalizing the inverse BP pattern. Thus, animal models of hypertension may help to better understand the mechanisms of BP regulation and to improve anti-hypertensive drug treatment. This notion is supported by clinical studies using ambulatory blood pressure monitoring in a cross-over design with morning versus evening drug dosing: In essential hypertensives morning dosing of enalapril is preferable to evening dosing, whereas in nocturnal hypertension due to chronic renal failure only evening dosing of isradipine (Portaluppi et al, Hypertension, in press) normalized the disturbed BP rhythm.