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Early gestation dexamethasone alters baroreflex and vascular responses in newborn lambs before hypertension. Am J Physiol Regul Integr Comp Physiol 2006 Aug;291(2):R481-8

Date

08/18/2006

Pubmed ID

16914435

DOI

10.1152/ajpregu.00677.2005

Scopus ID

2-s2.0-33745806160   29 Citations

Abstract

Exposure of the early gestation ovine fetus to exogenous glucocorticoids induces alterations in postnatal cardiovascular physiology, including hypertension. To determine whether autonomic function and systemic vascular reactivity are altered by in utero programming before the development of systemic hypertension, we examined arterial baroreflex function and in vivo hemodynamic and in vitro vascular responses to vasoactive agents in 10- to 14-day-old newborn lambs exposed to early gestation glucocorticoids. Dexamethasone (Dex, 0.28 mg.kg-1.day-1) or saline was administered to pregnant ewes by intravenous infusion over 48 h beginning at 27 days gestation (term 145 days), and lambs were allowed to deliver (n=6 in each group). Resting mean arterial blood pressure (MABP; 77+/-1 vs. 74+/-3 mmHg) and heart rate (HR; 249+/-9 vs. 226+/-21 beats/min) were similar in Dex-exposed and control animals, respectively. The arterial baroreflex curve, relating changes in HR to MABP, was significantly shifted toward higher pressure in the Dex-exposed lambs although no change in the sensitivity (gain) of the response was seen. In vivo changes in blood pressure in response to bolus doses of ANG II (20, 50, and 100 ng/kg) and phenylephrine (2, 5, and 10 microg/kg) were similar in the two groups. However, Dex lambs displayed greater decreases in MABP in response to ganglionic blockade with tetraethylammonium bromide (10 mg/kg; -30+/-3 vs. -20+/-3 mmHg, P<0.05) and greater increases in MABP after nitric oxide synthase blockade with NG-nitro-L-arginine (25 mg/kg; 23+/-3 vs. 13+/-2 mmHg, P<0.05) compared with control lambs. By in vitro wire myography, mesenteric and femoral artery microvessel contractile responses to KCl were similar, whereas responses to endothelin (in mesenteric) and norepinephrine (in femoral) were significantly attenuated in Dex lambs compared with controls. Femoral vasodilatory responses to forskolin and sodium nitroprusside were similar in the two groups (n=4). These findings suggest that resetting of the baroreflex, accompanied by increased sympathetic activity and altered nitric oxide-mediated compensatory vasodilatory function, may be important contributors to programming of hypertension.

Author List

Segar JL, Roghair RD, Segar EM, Bailey MC, Scholz TD, Lamb FS

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Animals, Newborn
Baroreflex
Blood Pressure
Dexamethasone
Female
Gestational Age
Heart Rate
Hypertension
Injections, Intravenous
Male
Maternal Exposure
Models, Animal
Phenylephrine
Pregnancy
Sheep
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75