Maternal low-protein diet during mouse pre-implantation development induces vascular dysfunction and altered renin-angiotensin-system homeostasis in the offspring.
Environmental perturbations during early mammalian development can affect aspects of offspring growth and cardiovascular health. We have demonstrated previously that maternal gestational dietary protein restriction in mice significantly elevated adult offspring systolic blood pressure. Therefore, the present study investigates the key mechanisms of blood pressure regulation in these mice. Following mating, female MF-1 mice were assigned to either a normal-protein diet (NPD; 18 % casein) or an isocaloric low-protein diet throughout gestation (LPD; 9 % casein), or fed the LPD exclusively during the pre-implantation period (3.5 d) before returning to the NPD for the remainder of gestation (Emb-LPD). All offspring received standard chow. At 22 weeks, isolated mesenteric arteries from LPD and Emb-LPD males displayed significantly attenuated vasodilatation to isoprenaline (P = 0.04 and P = 0.025, respectively), when compared with NPD arteries. At 28 weeks, stereological analysis of glomerular number in female left kidneys revealed no significant difference between the groups. Real-time RT-PCR analysis of type 1a angiotensin II receptor, Na+/K+ ATPase transporter subunits and glucocorticoid receptor expression in male and female left kidneys revealed no significant differences between the groups. LPD females displayed elevated serum angiotensin-converting enzyme (ACE) activity (P = 0.044), whilst Emb-LPD males had elevated lung ACE activity (P = 0.001), when compared with NPD offspring. These data demonstrate that elevated offspring systolic blood pressure following maternal gestational protein undernutrition is associated with impaired arterial vasodilatation in male offspring, elevated serum and lung ACE activity in female and male offspring, respectively, but kidney glomerular number in females and kidney gene expression in male and female offspring appear unaffected.
Watkins
Adam J
AJ
School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, UK. ajw7@soton.ac.uk
Lucas
Emma S
ES
Torrens
Christopher
C
Cleal
Jane K
JK
Green
Lauren
L
Osmond
Clive
C
Eckert
Judith J
JJ
Gray
William P
WP
Hanson
Mark A
MA
Fleming
Tom P
TP
D000818:Animals; D001158:Arteries; D001794:Blood Pressure; D001993:Bronchodilator Agents / Q000494:pharmacology; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D005260:Female; D006706:Homeostasis; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D007678:Kidney Glomerulus; D008168:Lung / Q000378:metabolism; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008643:Mesentery; D051379:Mice; D008815:Mice, Inbred Strains; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects; D011488:Protein Deficiency; D044140:Receptor, Angiotensin, Type 1; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D000254:Sodium-Potassium-Exchanging ATPase; D014664:Vasodilation
D001993:Bronchodilator Agents; D044140:Receptor, Angiotensin, Type 1; D011965:Receptors, Glucocorticoid; D007703:Peptidyl-Dipeptidase A; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol