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Organs/Systems Potentially Involved In One Model Of Programmed Hypertension In Sheep
Author(s) -
Dodic Miodrag,
Baird Rebecca,
Hantzis Vicky,
Koukoulas Irene,
Moritz Karen,
Peers Arianne,
Wintour E Marelyn
Publication year - 2001
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2001.03556.x
Subject(s) - medicine , endocrinology , offspring , blood pressure , angiotensin ii receptor type 1 , renin–angiotensin system , kidney , dexamethasone , fetus , medulla oblongata , angiotensin ii , pregnancy , biology , central nervous system , genetics
SUMMARY 1. When pregnant ewes and their fetuses are exposed to the synthetic glucocorticoid dexamethasone for 2 days early in pregnancy (days 26–28; term 145–150 days), female offspring have increased blood pressure relative to a control group. In one series, this was shown to be due to increased cardiac output, concomitant with a reset mean arterial pressure/heart rate reflex. The first group of such animals had, by the age of 7 years, left ventricular hypertrophy and reduced cardiac functional capacity. 2. The elevation in blood pressure is not maintained by any change in the peripheral renin–angiotensin system (RAS). 3. There is, however, preliminary evidence that some aspects of local RAS (particularly in the kidney and brain) could have participated in the ‘programming’ event. The levels of mRNA for angiotensin II receptors (AT 1 , AT 2 ) and angiotensinogen are increased in the kidney of such dexamethasone‐treated fetuses in late gestation (130 days), some 100 days after steroid treatment. Similar increases in AT 1 mRNA in the medulla oblongata of the fetal brain and large increases of mRNA for angiotensinogen occur in the hypothalamus. 4. These findings, together with evidence from the literature, suggest that both the kidney and parts of the brain are affected by events that also ‘program’ high blood pressure in the offspring of animals in which the intra‐uterine environment has been perturbed at some stage.