Altered vascular contractility in adult female rats with hypertension programmed by prenatal glucocorticoid exposure.
Excessive exposure to glucocorticoids during gestation reduces birth weight and induces permanent hypertension in adulthood. The mechanisms underlying this programmed elevation of blood pressure have not been established. We hypothesised that prenatal glucocorticoid exposure may lead to vascular dysfunction in adulthood. Pregnant rats received dexamethasone (Dex) (100 microg/kg, s.c.) or vehicle (control) daily throughout pregnancy. Blood pressure was elevated (students t-test, unpaired; P < 0.05) in adult female offspring (aged 12-16 weeks) of Dex-treated mothers (148.0 +/- 3.6 mmHg, n=10) compared with the control group (138.0 +/- 2.5 mmHg, n=8). Vascular responsiveness in aortae and mesenteric arteries was differentially affected by prenatal Dex: aortae were less responsive to angiotensin II, whereas mesenteric arteries were more responsive to norepinephrine, vasopressin and potassium (mesenteric arteries respond poorly to angiotensin II in vitro). Acetylcholine-mediated, endothelium-dependent relaxation was similar in both groups. Prenatal exposure to Dex had no effect on blood pressure or aldosterone response to acute (15 min, i.v.) infusion of angiotensin II (75 ng/kg per min). In contrast, chronic (2-week, s.c.) infusion of angiotensin II (100 ng/kg per min) produced a greater elevation (P < 0.05) of blood pressure in Dex-treated rats (150.0 +/- 3.6 mmHg) than in controls (135.3 +/- 5.4 mmHg), and aldosterone levels were higher in Dex-treated animals. There was no angiotensin II-induced medial hypertrophy/hyperplasia in mesenteric arteries from Dex-treated rats. These results indicate that vascular function is altered in a region-specific manner in rats with glucocorticoid-programmed hypertension. Despite a striking increase in mesenteric artery contraction in Dex-treated rats, in vivo studies suggest that abnormalities of the renin-angiotensin-aldosterone system, rather than enhanced vascular contractility, may be responsible for the elevation of blood pressure in these animals.
Hadoke
P W F
PW
Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK. phadoke@staffmail.ed.ac.uk
Lindsay
R S
RS
Seckl
J R
JR
Walker
B R
BR
Kenyon
C J
CJ
D000109:Acetylcholine / Q000494:pharmacology; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006973:Hypertension / Q000196:embryology* / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D007260:Infusion Pumps; D008638:Mesenteric Arteries / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects*
D005938:Glucocorticoids; D000804:Angiotensin II; D000450:Aldosterone; D003907:Dexamethasone; D012083:Renin; D000109:Acetylcholine; D003345:Corticosterone