Protein restriction during pregnancy induces hypertension and impairs endothelium-dependent vascular function in adult female offspring.
Intrauterine undernutrition plays a role in the development of adult hypertension. Most studies are done in male offspring to delineate the mechanisms whereby blood pressure may be raised; however, the vascular mechanisms involved in female offspring are unclear. Female offspring of pregnant Sprague-Dawley rats fed either a control (C; 18%) or a low-protein (LP; 6%) diet during pregnancy were used. Birth weight and later growth were markedly lower in LP than in C offspring. LP offspring exhibited impaired estrous cyclicity with increased mean arterial pressure. Hypotensive response to acetylcholine (ACh) and the hypertensive response to phenylephrine (PE) were greater in LP than in C rats. N-nitro-L-arginine methyl ester (L-NAME) induced greater hypertensive responses in C than in LP rats. Endothelium-intact mesenteric arteries from LP offspring exhibited increased contractile responses to PE and reduced vasodilation in response to ACh. In endothelium-denuded arteries, relaxation responses to sodium nitroprusside were similar in both groups. Basal and ACh-induced increase in vascular nitrite/nitrate production was lower in LP than in C offspring. L-NAME or 1H-1,2,4-oxadiazolo-4,3-quinoxalin-1-one inhibited ACh relaxations and enhanced PE contractions in C offspring, but had minimal effect in LP rats. The decreased NO-mediated vascular response might explain the increased vascular contraction and arterial pressure in female offspring with low birth weight.
Sathishkumar
Kunju
K
Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-1062, USA.
Elkins
Rebekah
R
Yallampalli
Uma
U
Yallampalli
Chandra
C
D000818:Animals; D001724:Birth Weight; D001794:Blood Pressure; D004044:Dietary Proteins / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000502:physiology*; D004971:Estrus; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006973:Hypertension / Q000209:etiology*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction; D014664:Vasodilation
D004044:Dietary Proteins; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester