Pregnancy prevents hypertensive remodeling of cerebral arteries: a potential role in the development of eclampsia.
We investigated how hypertension during pregnancy affected passive structural (wall:lumen, wall stress) and active (myogenic activity) responses of the cerebral circulation. Female nonpregnant (NP; n=8) Sprague Dawley rats were compared with late-pregnant (LP; day 19 to 20, n=6) rats. Some animals were treated with the NO synthase inhibitor nitro-L-arginine in their drinking water to raise blood pressure. LP rats (n=6) were treated for the last 7 days of pregnancy (last trimester) to mimic preeclampsia and compared with NP rats treated for the same duration (n=8). Active and passive responses were determined on isolated and pressurized third-order posterior cerebral arteries. Nitro-L-arginine treatment significantly raised blood pressure in both groups of animals that was associated with increased wall thickness and wall:lumen ratio in the NP hypertensive animals versus controls (P<0.05). In contrast, this response to pressure was absent in LP animals, which had similar wall measurements. In addition, arteries from NP hypertensive animals had increased myogenic tone and pressure of forced dilatation compared with NP control animals (P<0.01). Again, this response was lacking in the LP hypertensive animals that had similar tone and pressure of forced dilatation as normotensive controls. The increased tone and wall thickness decreased wall stress in the NP hypertensive animals, a response that did not occur in LP hypertensive animals. Because medial hypertrophy is considered a protective response to elevated blood pressure, these results suggest that hypertension in pregnancy may predispose the cerebral circulation to autoregulatory breakthrough and blood-brain-barrier disruption when blood pressure is elevated, as during eclampsia.
Cipolla
Marilyn J
MJ
Department of Neurology, University of Vermont, Burlington, VT 05405, USA. Marilyn.Cipolla@uvm.edu
DeLance
Nicole
N
Vitullo
Lisa
L
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier; D002536:Cerebral Arteries / Q000473:pathology / Q000503:physiopathology*; D004461:Eclampsia / Q000209:etiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D006706:Homeostasis; D006973:Hypertension / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D018715:Microscopy, Video; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000139:chemically induced / Q000503:physiopathology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D019001:Nitric Oxide Synthase