Spironolactone improves structure and increases tone in the cerebral vasculature of male spontaneously hypertensive stroke-prone rats.
BACKGROUND
Previous studies show that ischemic cerebral infarct size is related to cerebral vessel structure. Spironolactone, a mineralocorticoid receptor antagonist, decreases ischemic cerebral infarct size in male spontaneously hypertensive stroke-prone rats (SHRSP). Therefore, we hypothesized that chronic spironolactone treatment would improve cerebral artery structure in the SHRSP.


METHODS
Six-week-old male SHRSP were treated with spironolactone (2.5 mg/day) for 6 weeks and were compared to untreated control SHRSP and normotensive Wistar Kyoto (WKY) rats. Using a pressurized arteriograph, structural measurements of the middle cerebral artery (MCA) were taken under passive (calcium-free), zero-flow conditions. Myogenic tone was calculated from active and passive measurements taken at 75 and 125 mmHg. Mean arterial pressure was measured using radiotelemetry.


RESULTS
Myogenic tone was increased only at 75 mmHg in the spironolactone-treated SHRSP compared to control rats. The MCA lumen and outer diameters were increased in the spironolactone-treated SHRSP compared to control SHRSP, but were not different from WKY rats, indicating a decrease in vascular remodeling. There was no effect of spironolactone on blood pressure, suggesting that this is a blood pressure-independent effect.


CONCLUSIONS
Increased myogenic tone and lumen diameter in the spironolactone-treated SHRSP may be responsible for the protective role of spironolactone in ischemic stroke.
Rigsby
Christine' S
CS
Department of Physiology, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-3000, USA. cshnjrr@hotmail.com
Pollock
David M
DM
Dorrance
Anne M
AM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003187:Compliance / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000494:pharmacology; D013148:Spironolactone / Q000494:pharmacology* / Q000627:therapeutic use; D020521:Stroke / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D013686:Telemetry; D013997:Time Factors
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D012701:Serotonin