No abstract

No abstract

In models that describe the homeostasis of the circulation, arterial blood pressure is usually expressed as a single value, which is regarded as the set point in such systems. The aim of the study was to identify in rats from 24-h beat-to-beat recordings the value of blood pressure that describes best such a set point of the cardiovascular system. Normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), kept on a 12:12-h lights on-off cycle, were instrumented for computerized 24-h beat-to-beat recording of mean arterial pressure (MAP) and pulse interval (PI). Three-dimensional frequency distributions were constructed by plotting for each beat its MAP vs. its PI. During the dark period, the concurrent distribution of MAP and PI showed two distinct modes while during the light period a single mode was found. Comparable patterns were found in SHRs and WKYs. These three different modes were significantly different from the mathematically calculated mean values of MAP and PI over these periods. Thus in rats the 24-h behavior of the cardiovascular system is better described by dynamic shifts between different modes (homeodynamic states) than by a single set point.

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.

Atrial natriuretic factor (ANF) lowers blood volume in intact and anephric experimental animals. The latter observation suggests extravasation of plasma at the level of the microcirculation. In view of the differential regional hemodynamic responses to ANF, the present study investigates possible regional differences in plasma extravasation measured as regional albumin clearances in skeletal muscle, lung, brain, ileum, and skin. In control animals, there were pronounced regional differences in clearances with highest values in ileum (0.248 +/- 0.015 microliter/min.g tissue) and lowest in brain (0.010 +/- 0.002 microliter/min.g tissue). Plasma-volume was 3.58 +/- 0.07 ml/100 g b.w. ANF (1 microgram/kg.min) significantly reduced plasma-volume (3.20 +/- 0.06 ml/100 g b.w.). This was associated with significantly increased albumin clearances in skeletal muscle and ileum, but not in other tissues examined. The data indicate that ANF increases albumin extravasation. This suggests that, besides effects on renal function and vascular tone, ANF also affects blood volume through influencing the relationship between intra- and extravascular volume.