Role of 20-HETE,TRP channels & BKCa in dysregulation of pressure-induced Ca2+ signaling and myogenic constriction of cerebral arteries in aged hypertensive mice.

Role of 20-HETE,TRP channels & BKCa in dysregulation of pressure-induced Ca2+ signaling and myogenic constriction of cerebral arteries in aged hypertensive mice. Am J Physiol Heart Circ Physiol. 2013 Oct 4; Authors: Toth P, Csiszar A, Tucsek Z, Sosnowska D, Gautam T, Koller A, Laniado Schwartzman M, Sonntag WE, Ungvari ZI Abstract Hypertension in the elderly substantially increases the risk 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) C57BL/6 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 S...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research