Genetic predisposition to hypertension sensitizes borderline hypertensive rats to the hypertensive effects of prenatal glucocorticoid exposure.
An adverse intrauterine environment can increase the incidence of hypertension and other cardiovascular disease risk factors. However, in clinical and experimental studies the magnitude of the effect is variable. Possibly, the relative influence of the prenatal environment on cardiovascular disease is determined in part by genetic factors that predispose individuals to the development of environmentally induced hypertension. We tested this hypothesis by comparing the effects of prenatal dexamethasone treatment (Dex, 300 microg kg(-1) i.p. on days 15 and 16 of gestation) in borderline hypertensive rats (BHR) and control Wistar-Kyoto (WKY) rats. Blood pressure, heart rate and plasma corticosterone values were measured at rest during the middle of the day, and during 1 h of restraint stress in the adult offspring using indwelling arterial catheters implanted at least 4 days prior to data collection. Compared with the saline (vehicle) control treatment, prenatal dexamethasone significantly (P < 0.05) increased baseline mean arterial pressure in male (123 +/- 2 versus 131 +/- 3 mmHg, saline versus Dex) and female (121 +/- 2 versus 130 +/- 2 mmHg, saline versus Dex) BHR, but not in male (108 +/- 3 versus 113 +/- 2 mmHg, saline versus Dex) or female (112 +/- 2 versus 110 +/- 2 mmHg, saline versus Dex) WKY rats. Relative to saline treatment, prenatal Dex also significantly increased baseline heart rate (328 +/- 6 versus 356 +/- 5 beats min(-1), saline versus Dex) and plasma corticosterone (5 +/- 2 versus 24 +/- 4 microg dl(-1), saline versus Dex), and prolonged the corticosterone response to acute stress, selectively in female BHR. However, prenatal Dex significantly enhanced the arterial pressure response to acute stress only in female WKY, while Dex augmented the elevation in heart rate during stress only in male rats. We conclude that prenatal dexamethasone increased baseline arterial pressure selectively in BHR, and plasma corticosterone only in female BHR. In contrast, prenatal Dex enhanced cardiovascular reactivity to stress in both BHR and WKY rats.
Bechtold
Andrea G
AG
Department of Medical Pharmacology, University of California, Davis, Davis, CA 95616, USA.
Vernon
Kathy
K
Hines
Tina
T
Scheuer
Deborah A
DA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D020022:Genetic Predisposition to Disease; D005938:Glucocorticoids / Q000009:adverse effects* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics*; D007328:Insulin / Q000097:blood; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012307:Risk Factors; D013312:Stress, Physiological / Q000503:physiopathology
D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D003907:Dexamethasone; D003345:Corticosterone