Abstract
Genetic susceptibility is an important factor in raising blood pressure (BP). Daily (circadian) rhythm characteristics are considered essential parameters for recognizing and treating increased risks in BP. To examine BP in genetics with environmental modifications, one-cell homozygous embryos were transferred into spontaneously hypertensive (SHR, pup:shr) or normotensive (WKY, pup:wky) rats' oviducts (embryos: s, w; oviduct-uterine: S, W) in a reciprocal fashion. Pups were cross-suckled at birth (nurses S, W) and weaned to normal diets at day-21. At Day-120, telemetered BPs were monitored for 5 consecutive days every 4 min and analyzed by the method of ANOVA. Ambulatory BP in 20 adolescents and adults were monitored automatically around the clock at 30-min to hourly intervals and analyzed by the least square rhythmometry method. As expected, shr BPs were markedly reduced when they were transplanted to the W-uterine and/or the W-lactation milieu (sSS vs. sSW, sWS and sWW: 197 vs.178, 147 and 178 mm Hg). BP in wky was significantly altered only in the wSW group (wWW vs, wSW: 127 vs.131 mm Hg). All subjects showed significant circadian fluctuations with a peak in the late afternoon hours in most human subjects and rats as a nocturnal animal mostly close to midnight hours, while shr with W-uterine (sWS) a bit delayed peak hour (00:45) and with combined W-uterine/W-nursing (sWW) a bit earlier peak hour (20:12). Circadian double amplitudes (2A) in the human subjects 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 as compared to that of wWW (7.5±0.7 for sSS, 8.3±0.6 for sSW vs. 4.7±0.3 mm Hg for wWW). The hypertensive-prone shr strain showed significantly lowered BPs in a normotensive WKY uterine environment and/or by WKY nursing mothers, indicating that environment influences can strongly modify genetic factors, yet the lowered shr MESORs by the WKY environments remained above the MESORs encountered in wky donors. Chronomes broader than circadian should be considered in interpreting BP responses as a gauge of vascular disease status.
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