The neurovascular dysfunction induced by angiotensin II in the mouse neocortex is sexually dimorphic.
Women are less susceptible to the cerebrovascular complications of hypertension, such as a stroke and vascular dementia. The mechanism of such protection may be related to a reduced vulnerability of women to the cerebrovascular actions of hypertension. To test this hypothesis, we used a model of hypertension based on infusion of angiotensin II (ANG II), an octapeptide that plays a key role in hypertension and produces cerebrovascular dysregulation. Cerebral blood flow (CBF) was monitored by laser-Doppler flowmetry in anesthetized (urethane-chloralose) C57BL/6J male and female mice equipped with a cranial window. ANG II administration (0.25 mug.kg(-1).min(-1) iv x 30-45 min) elevated arterial pressure equally in both sexes but attenuated the CBF increase induced by whisker stimulation or by the endothelium-dependent vasodilator acetylcholine (ACh) in male but not in female mice. The administration of ANG II for 7 days (2.74 mg.kg(-1).day(-1)), using osmotic minipumps, also attenuated these cerebrovascular responses in male, but not female, mice. The reduced susceptibility to the effect of ANG II in female mice was abolished by ovariectomy and reinstated by estrogen administration to ovariectomized mice. Administration of estrogen to male mice abolished the ANG II-induced attenuation of CBF responses. We conclude that female mice are less susceptible to the cerebrovascular dysregulation induced by ANG II, an effect related to estrogen. Such protection from the deleterious cerebrovascular effects of hypertension may play a role in the reduced vulnerability to the cerebrovascular complications of hypertension observed in women.
Girouard
H
H
Division of Neurobiology, Weill Cornell Medical College, 411 E. 69th Street, New York, NY 10021, USA.
Lessard
A
A
Capone
C
C
Milner
T A
TA
Iadecola
C
C
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism*; D015914:Estrogen Replacement Therapy; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D015918:Infusion Pumps, Implantable; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D010052:Ovariectomy; D012018:Reflex; D012737:Sex Factors; D020521:Stroke / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology; D014738:Vibrissae / Q000294:innervation
D014665:Vasodilator Agents; D000804:Angiotensin II; D004958:Estradiol; D000241:Adenosine; D000109:Acetylcholine