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 in hibit the renin-angiotensin system can be used to blunt the rise in blood p ressure that occurs during the transition from the resting to the active pe riod of the day. For this purpose we compared in spontaneously hypertensive rats (SHR) the antihypertensive efficacy of the angiotensin converting enz yme (ACE) inhibitors captopril (doses: 3, 10, and 30 mg/kg/6 h) and enalapr ilat (0.3 mg/kg/6 h), and the AT(1)-receptor antagonist losartan (10 mg/kg/ 6 h) at two different treatment regimens. The antihypertensive drugs were g iven as a continuous 6-h infusion either during the transition from the dar k to light period (DL) or that from the light to dark period (LD) for 5 con secutive days. For all agents, the average 24-h reduction of blood pressure was comparable for the LD or DL treatment regimen. However, the dynamics o f the antihypertensive response were markedly different. The increase in bl ood pressure at awakening could be blunted much more effectively by the LD than DL treatment regimen. Furthermore, as indicated by the trough:peak rat ios, blood pressure profiles were flatter with the LD than with the DL regi men. 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. (C) 1999 American Journal of Hyperte nsion, Ltd.