Abstract 036: Genetics and Epigenetics on Circadian Blood Pressure and Variability in Rats Compared With Ambulatory Blood Pressure Variability in Human

Hypertension is associated with high morbidity and mortality. Blood pressure (BP) levels vary widely due to predictable biological rhythms and unpredictable environmental factors. Daily (circadian) rhythm characteristics are considered essential parameters for recognizing and treating increased risks in BP. Franz Halberg spent most of his academic career in cardiovascular research, focused on ambulatory monitoring and developing chronobiological methods for clinical application. To compare BP Variability (BPV), automatically monitored ambulatory BP around the clock at 30-60 min intervals in 20 human subjects was compared with telemetered circadian BP in rats after one-cell homozygous embryo-transfer into spontaneously hypertensive (SHR, pup:shr) or normotensive (WKY, pup:wky) rats' oviducts (embryos: s,w; oviduct-uterus: S,W) and cross-suckled at birth (nurses S,W). The circadian response peaked in the late afternoon hours in most human subjects and early morning hours in rats. Human circadian double amplitudes (2A) varied from 8 to 26 mm Hg with higher 2A in elder adults, and 3-8 mm Hg in rats with significantly higher fluctuations in SHR groups (7.5±0.7 for sSS, 8.3±0.6 for sSW vs. 4.7±0.3 mm Hg for wWW). The circaseptan 2A in the adolescents were 10±1 for SBP and 12±3 mm Hg for DBP, and sharp increased winter 2A (SBP 54; HR 48, both P<0.0001) were observed. In rats, mostly clustered peaks around the light-on hours, while sWS and wSS groups showed peak-hour variations (19:18 to 08:06 and 02:58 to 09:10 hrs, respectively). The peak-hour in shr strains was shifted to earlier or delayed in the WKY uterus (sWW and sWS groups) with large deviations as compared to the wWW group. Hypertensive-prone shr strains showed significantly lowered BPs in WKY uterine and/or WKY nursing environments indicating that environment can strongly modify genetic influence, yet the lowered shr MESORs by the WKY environments remained above the MESORs encountered in wky donors. Thus, the maternal environment may be a major factor that affects the offspring’s BP and BPV later in life. Chronomes broader than circadian BPs are considered as a gauge of vascular disease status. Abnormal BP/BPV modifications may lead to novel implications in preventive and therapeutic strategies in CVD.