Timed inhibition of the renin-angiotensin system suppresses the rise in blood pressure upon awakening in spontaneously hypertensive rats

In this study we investigated whether timed administration of drugs that inhibit the renin-angiotensin system can be used to blunt the rise in blood pressure that occurs during the transition from the resting to the active period of the day. For this purpose we compared in spontaneously hypertensive rats (SHR) the antihypertensive efficacy of the angiotensin converting enzyme (ACE) inhibitors captopril (doses: 3, 10, and 30 mg/kg/6 h) and enalaprilat (0.3 mg/kg/6 h), and the AT1-receptor antagonist losartan (10 mg/kg/6 h) at two different treatment regimens. The antihypertensive drugs were given as a continuous 6-h infusion either during the transition from the dark to light period (DL) or that from the light to dark period (LD) for 5 consecutive days. For all agents, the average 24-h reduction of blood pressure was comparable for the LD or DL treatment regimen. However, the dynamics of the antihypertensive response were markedly different. The increase in blood pressure at awakening could be blunted much more effectively by the LD than DL treatment regimen. Furthermore, as indicated by the trough:peak ratios, blood pressure profiles were flatter with the LD than with the DL regimen. Thus, in SHR, 24-h rhythms of blood pressure can be modulated by timed administration of ACE inhibitors and losartan, such that the early morning rise in blood pressure is suppressed.