Antiadhesion Molecule Therapy for Refractory Vasculitis: Experience in Five Patients Treated with Humanised Monoclonal anti CD18 Antibodies

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 (AT1, AT2) 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 AT1 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.

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Organs/Systems Potentially Involved In One Model Of Programmed Hypertension In Sheep

Dodic

Baird

Hantzis

et al. 2001

Clin Exp Pharma Physio

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Different Etiologies of Intrauterine Growth Restriction and Different Consistencies in the Occurrence of Abnormal Local Nonstationarity of Fetal Heart Rate

Yum

Kim

Park

et al. 2006

Clinical and Experimental Hypertension

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Fetuses with intrauterine growth restriction (IUGR) can be programmed in utero to develop hypertension in adult life. The etiology of IUGR in human fetuses is not uniform. The present study demonstrated that different etiologies of growth restriction, idiopathic cause, and pregnancy-induced hypertension, produce different consistencies in the occurrence of an abnormal local very-short-term nonstationarity of heart rate during intrauterine period. Whether the consistent abnormality that was found in the growth-restricted fetuses associated with pregnancy-induced hypertension is linked to the different risk of later hypertension requires future studies.

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Impaired Cardiac Functional Reserve and Left Ventricular Hypertrophy in Adult Sheep After Prenatal Dexamethasone Exposure

Dodic

Samuel

Moritz

et al. 2001

Circulation Research

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Abstract-We have shown that exposure of pregnant ewes to dexamethasone (11.5 mg/d for 2 days) at 27 days of gestation (term, 150 days) led to increased blood pressure and cardiac output in adult offspring. In this study, we hypothesized that dexamethasone-induced hypertension is associated with left ventricular hypertrophy and a reduced cardiac functional reserve (CO max-0 ). Six control animals (group C) and five dexamethasone-exposed animals (group D) were volume-loaded with Hemaccel until the wedge pressure was 13 mm Hg (baseline). The wedge pressure was held constant during an infusion of dobutamine at incremental doses (0.4 to 12 g/kg/min) while blood pressure and cardiac output were measured. here is now strong and coherent epidemiological evidence that reduced growth in utero and in years 1 through 5 is linked with higher incidence of known cardiovascular risk factors, including hypertension, non-insulin-dependent diabetes mellitus, raised serum lipids, increased left ventricular mass, and reduced arterial compliance in later life.

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Antiadhesion Molecule Therapy for Refractory Vasculitis: Experience in Five Patients Treated with Humanised Monoclonal anti CD18 Antibodies

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Organs/Systems Potentially Involved In One Model Of Programmed Hypertension In Sheep

Organs/Systems Potentially Involved In One Model Of Programmed Hypertension In Sheep

Different Etiologies of Intrauterine Growth Restriction and Different Consistencies in the Occurrence of Abnormal Local Nonstationarity of Fetal Heart Rate

Impaired Cardiac Functional Reserve and Left Ventricular Hypertrophy in Adult Sheep After Prenatal Dexamethasone Exposure

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