Mineralocorticoid receptor activation causes cerebral vessel remodeling and exacerbates the damage caused by cerebral ischemia.
Mineralocorticoid receptor antagonists protect against ischemic cerebrovascular disease; this appears to be caused by changes in cerebral vessel structure that would promote blood flow. Therefore, we hypothesized that mineralocorticoid receptor activation with deoxycorticosterone acetate would cause deleterious remodeling of the cerebral vasculature and exacerbate the damage caused by cerebral ischemia. Six-week-old male Wistar rats were treated with deoxycorticosterone acetate (200 mg/kg) for 6 weeks. At 12 weeks of age, the deoxycorticosterone acetate-treated rats had elevated systolic blood pressure compared with age-matched controls (157+/-5.9 versus 124+/-3.1 mm Hg deoxycorticosterone acetate versus control; P<0.05). The area of ischemic damage resulting from middle cerebral artery occlusion was greater in the deoxycorticosterone acetate-treated rats than control (63.5+/-3.72 versus 46.6+/-5.52% of the hemisphere infarcted, deoxycorticosterone acetate versus control; P<0.05). Middle cerebral artery structure was assessed using a pressurized arteriograph under calcium-free conditions. Over a range of intralumenal pressures, the lumen and ODs of the middle cerebral arteries were smaller in the deoxycorticosterone acetate-treated rats than the control rats (P<0.05). There was also an increase in the wall thickness and wall:lumen ratio in the vessels from deoxycorticosterone acetate-treated rats (P<0.05). The vessels from the deoxycorticosterone acetate-treated rats were stiffer than those from control rats as evidenced by a leftward shift in the stress/strain curve. These novel data suggest that mineralocorticoid receptor activation without salt loading and nephrectomy is sufficient to elicit deleterious effects on the cerebral vasculature that lead to inward hypertrophic remodeling and an increase in the ischemic damage in the event of a stroke.
Dorrance
Anne M
AM
Department of Physiology, Medical College of Georgia, Augusta, GA 30912-3000, USA. adorrance@.mcg.edu
Rupp
Nikki C
NC
Nogueira
Edson F
EF
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000503:physiopathology; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology*; D002544:Cerebral Infarction / Q000473:pathology; D003900:Desoxycorticosterone / Q000494:pharmacology*; D008297:Male; D018715:Microscopy, Video; D020768:Middle Cerebral Artery / Q000473:pathology; D011188:Potassium / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000187:drug effects* / Q000378:metabolism*
D018161:Receptors, Mineralocorticoid; D003900:Desoxycorticosterone; D011188:Potassium