Prenatal dexamethasone 'programmes' hypotension, but stress-induced hypertension in adult offspring.
Low birth weight in humans is predictive of hypertension in adult life. Although the mechanisms underlying this link remain unknown, fetal overexposure to glucocorticoids has been implicated. We previously showed that prenatal dexamethasone (DEX) exposure in the rat lowers birth weight and programmes adult hypertension. The current study aimed to further investigate the nature of this hypertension and to elucidate its origins. Unlike previous studies, we assessed offspring blood pressure (BP) with radiotelemetry, which is unaffected by stress artefacts of measurement. We show that prenatal DEX during the last week of pregnancy results in offspring of low birth weight (14% reduction) that have lower basal BP in adulthood ( approximately 4-8 mmHg lower); with the commonly expected hypertensive phenotype only being noted when these offspring are subjected to even mild disturbance or a more severe stressor (up to 30 mmHg higher than controls). Moreover, DEX-treated offspring sustain their stress-induced hypertension for longer. Promotion of systemic catecholamine release (amphetamine) induced a significantly greater rise of BP in the DEX animals (77% increase) over that observed in the vehicle controls. Additionally, we demonstrate that the isolated mesenteric vasculature of DEX-treated offspring display greater sensitivity to noradrenaline and other vasoconstrictors. We therefore conclude that altered sympathetic responses mediate the stress-induced hypertension associated with prenatal DEX programming.
O'Regan
David
D
Endocrinology Unit, Queen's Medical Research Institute, Centre for Cardiovascular Science, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Kenyon
Christopher J
CJ
Seckl
Jonathan R
JR
Holmes
Megan C
MC
D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D001808:Blood Vessels / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects*; D006128:Growth; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000209:etiology*; D007022:Hypotension / Q000139:chemically induced*; D008297:Male; D008643:Mesentery / Q000098:blood supply; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D013268:Stimulation, Chemical; D013312:Stress, Physiological / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D015430:Weight Gain / Q000187:drug effects
D002395:Catecholamines; D005938:Glucocorticoids; D003907:Dexamethasone