TIME-DEPENDENT EFFICACY OF ANTIHYPERTENSIVE AGENTS IN SPONTANEOUSLY HYPERTENSIVE RATS

The efficacy of antihypertensive agents was compared when given at different time points in the circadian rhythm. Spontaneously hypertensive rats (SHRs) were kept on a 12/12-h cycle with lights on/off at 07:00/ 19:00 h. A computerized system was used to measure intraarterial blood pressure and heart rate continuously. Agents or vehicle were intravenously injected at two time points. One at the beginning of the sleeping period, at which low efficacy was expected (T = 10), and one at T = 16, which is 3 h before the circadian peaks in blood pressure (BP) and heart rate (HR), aimed at reducing the rise in BP and HR at awakening. The hypotensive effect of propranolol, metoprolol, labetalol, prazosin, clonidine, and rilmenidine was greater when injected at T = 16 than at T = 10 (p < 0.05 for propranolol, metoprolol, and rilmenidine). In contrast, the renal vasodilators captopril and tertatolol were more potent after injection at T = 10. Felodipine was equally effective at both time points. Thus, the effects of antihypertensive agents are related to the phase of the circadian rhythm. The data on the sympatholytic agents in general and beta-blockers and centrally acting agents in particular support antihypertensive regimens with timed administrations.