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Stroke related alterations in protease activated receptor‐2 and bradykinin mediated vasodilation in the middle cerebral arteries of stroke prone hypertensive rats
Author(s) -
Smeda John Stanislaw,
McGuire John,
Daneshtalab Noriko
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.579.7
Subject(s) - bradykinin , vasodilation , losartan , medicine , endocrinology , captopril , mesenteric arteries , cerebral arteries , chemistry , angiotensin ii , pharmacology , blood pressure , receptor , artery
Vasodilation to bradykinin (1.2 µM) and protease‐activated receptor‐2 activation by 2‐furoyl‐leucine‐isoleucine‐glycine‐arginine‐leucine‐ornithine‐amide (2‐FLY, 1 µM) was measured in isolated pressurized (100 mmHg) middle cerebral arteries (MCAs) from Kyoto Wistar stroke prone spontaneously hypertensive rats (SHRsp) before and after hemorrhagic stroke (HS). Vasodilation to both peptides was endothelial dependent and produced by a non NO, cyclo‐oxygenase dependent mechanism that activated endothelial IK Ca +SK Ca channels and promoted vasodilation through smooth muscle BK Ca, K ir channels and Na + /K + ATPase activation. After HS, MCAs lacked the ability to vasodilate to bradykinin. Vasodilation to 2‐FLY was not altered. Post stroke oral Losartan (35 mg/kg/day) or Captopril (50 mg/kg/day) treatment did not reduce blood pressure. Losartan treatment restored MCA bradykinin vasodilation after 7 days for the duration of the study (>100 days treatment). Captopril only temporarily restored bradykinin relaxation between 7 to 25 days of treatment after which this function deteriorated. HS produced selective alterations in MCA endothelial function that could not be explained solely by the level of hypertension or as a secondary consequence of HS. These dysfunctions were reversed more effectively in SHRsp after HS by blocking AT‐1 receptors as opposed to lowering angiotensin II levels.