A Practical Approach, Second Edition=Ronald D. Ho.pdf

1070 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONAssociations between birth weight, childhood growth and blood pressure are reported bynumerous investigators (Georgieff et al., 1996; Uiterwaal et al., 1997; Walker et al., 2001). Therewas a significant correlation between systolic and diastolic blood pressure and both weight andlength at birth to 4 months of age (Georgieff et al., 1996). Greater weight gain between ages 7 and11 was associated with a greater increase in systolic blood pressure. The relation between growthand blood pressure is complex and has prenatal and postnatal components (Walker et al., 2001).Systolic blood pressure increased, with height, from 111 to 120 mm Hg in girls (body height 120to 180 cm), as well as in boys from 112 to 124 mm Hg (Steiss and Rascher, 1996). However, meandiastolic blood pressure did not change during maturation and was 72 to 74 mm Hg, irrespectiveof height and sex.The correlation coefficient between systolic and diastolic blood pressure increased steadily withage from 0.28 at 2 years to 0.59 at 10 years, but do not reach adult levels during this period (Levineet al., 1979; de Swiet et al., 1992).In adults, arterial baroreceptors are the major sensing elements of the cardiovascular system.In the majority of species, including humans, baroreceptor reflexes at birth exhibit depressedsensitivity with a gradual postnatal maturation to adult levels (Gootman et al., 1979; Vatner andManders, 1979).Comparative SpeciesThe heart rate in neonatal rats increases during the early postnatal period and then remains relativelyconstant into adulthood (Kyrieleis, 1963; Diez and Schwartze, 1991; Quigley et al., 1996). Thisincrease in rate appears to be inversely proportional to the decrease in QT interval seen during thisperiod, and may be explained by the increasing influence of the sympathetic system.Heart Rate of Postnatal Wistar Rats(Diez and Schwartze, 1991)Age (days)Heart Rate (beats/min)6 296 ± 6014 405 ± 3321 433 ± 4830 436 ± 3638 444 ± 2453 435 ± 27Hemodynamics in neonatal rats is characterized by a high cardiac output and low systemicresistance (Prewitt and Dowell, 1979). Shortly before puberty, there is a rise of systemic resistance,accompanied by a decrease in cardiac output (Smith and Hutchins, 1979). This is primarily due tostructural maturation of the vasculature. Developmental changes in vascular sensitivity to vasoactiveagents play a less important role for the maturational rise in systemic resistance. Marked maturationof the baroreceptor reflex also occurs during the postnatal period (Andresen et al., 1980). Normalsystolic blood pressure in the young rat is more than double that of the neonate and reaches adultlevels by 10 weeks of age (Litchfield, 1958; Gray, 1984; Rakusan et al., 1994).Blood Pressure in RatsAgeBlood Pressure (mm Hg)Newborn 15–253-4 Weeks of Age 80–95© 2006 by Taylor & Francis Group, LLC