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Dysregulation of pressure‐induced Ca 2+ signaling and myogenic constriction of cerebral arteries in aged hypertensive mice (1079.3)
Author(s) -
Toth Peter,
Csiszar Anna,
Tucsek Zsuzsanna,
Sosnowska Danuta,
Gautam Tripti,
Koller Akos,
Schwartzman Michal,
Sonntag William,
Ungvari Zoltan
Publication year - 2014
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.28.1_supplement.1079.3
Subject(s) - iberiotoxin , myogenic contraction , medicine , endocrinology , cerebral arteries , blood pressure , vascular smooth muscle , vasodilation , smooth muscle
Hypertension in the elderly substantially increases the risk of stroke and vascular cognitive impairment (VCI) in part due to an impaired functional adaptation of aged cerebral arteries to high blood pressure. To elucidate the mechanisms underlying impaired autoregulatory protection in aging, hypertension was induced in young (3 mo) and aged (24 mo) C57/BL6 mice by chronic infusion of angiotensin II and pressure‐induced changes in smooth muscle (SMC) [Ca 2+ ] i and myogenic constriction of middle cerebral arteries (MCA) were assessed. In MCAs from young hypertensive mice pressure‐induced increases in VSMC [Ca 2+ ] i and myogenic tone were increased and these adaptive responses were inhibited by the cytochrome P450 ω‐hydroxylase inhibitor HET0016 and the TRP channel blocker SKF96365. Administration of 20‐HETE increased SMC [Ca 2+ ] i and constricted MCAs and these responses were inhibited by SKF96365. MCAs from aged hypertensive mice did not show adaptive increases in pressure‐induced calcium signal and myogenic tone and responses to HET0016 and SKF96365 were blunted. Inhibition of BK channels by iberiotoxin enhanced SMC [Ca 2+ ] i and myogenic constriction in MCAs of young normotensive animals, whereas it was without effect in MCAs of young hypertensive mice. Iberiotoxin did not restore myogenic adaptation in MCAs of aged hypertensive mice. Thus, functional maladaptation of aged cerebral arteries to hypertension is due to the dysregulation of pressure‐induced, 20‐HETE and TRP channel‐mediated SMC calcium signaling, whereas overactivation of BK channels is unlikely to play a role in this phenomenon. Grant Funding Source : Supported by the American Heart Association and the Nemzeti Fejlesztési Ügynökség