Perinatal 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure sensitizes offspring to angiotensin II-induced hypertension.
In utero and lactational exposure of mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to cardiac hypertrophy and hydronephrosis in adulthood. We tested the hypothesis that perinatal TCDD exposure increases the susceptibility to cardiovascular disease when offspring are exposed to a common cardiovascular disease risk factor, angiotensin II (Ang II). Pregnant C57BL/6N mice were exposed to corn oil (control) or 6.0 microg/kg TCDD on gestation day 14.5. Male offspring were then exposed to a subpressor (0.1 mg/kg/day) or pressor (0.7 mg/kg/day) dose of Ang II at 3.5 months and cardiac morphology and blood pressure analyzed, respectively. Perinatal TCDD exposure increased left ventricular cavity dilation during diastole, and wall thickness during diastole and systole. While Ang II stimulated an increase in wall thickness, the degree of increase was equivalent between control and TCDD offspring. In contrast, perinatal TCDD exposure did not alter basal blood pressure. However, Ang II increased systolic blood pressure more rapidly and to a greater degree in TCDD offspring. Further, Ang II stimulated renal myofibroblast differentiation and collagen deposition to a greater degree, and tended to increase procollagen I mRNA in TCDD offspring, compared to controls. These data suggest that perinatal TCDD exposure increases the susceptibility of offspring to renal fibrosis and hypertension in adulthood.
Aragon
Andrea C
AC
College of Pharmacy, University of New Mexico, MSC09 5360, 2703 Frontier Ave, Suite 220, Albuquerque, NM, 87131-5691, USA.
Goens
M Beth
MB
Carbett
Eleanor
E
Walker
Mary K
MK
D000804:Angiotensin II; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D006332:Cardiomegaly / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005355:Fibrosis; D005865:Gestational Age; D006973:Hypertension / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D013686:Telemetry; D013997:Time Factors; D014463:Ultrasonography
D002274:Carcinogens, Environmental; D008562:Membrane Glycoproteins; D000072317:Polychlorinated Dibenzodioxins; D011347:Procollagen; D012333:RNA, Messenger; D000804:Angiotensin II; D003094:Collagen; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases