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Coupling of Coronary Blood Flow to Cardiac Metabolism: Role of TRPV1 Channels and Local Changes in pH
Author(s) -
Guarini Giacinta,
Ohanyan Vahagn A.,
Talasila Phani K.,
Bratz Ian N.
Publication year - 2011
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.25.1_supplement.1023.10
Subject(s) - trpv1 , vasodilation , medicine , chemistry , endocrinology , capsaicin , blood flow , microcirculation , cardiology , transient receptor potential channel , receptor
TRPV1 channels, known to be activated by noxious stimuli such as pH changes, are thought to play a role in the regulation of the vascular tone. Accordingly, we hypothesized that TRPV1 activation by local pH changes during increased metabolic demand and/or ischemia would lead to modulation of myocardial blood flow (MBF). Further we will examine if TRPV1 channel dysfunction could contribute to the microvascular impairment in diabetic cardiomyopathy. To test our hypothesis, control (C57/B6), db/db and TRPV1 null mice (TRPV1 −/− ) were subjected to contrast stress echocardiography for quantification of MBF at baseline and during the infusion of the TRPV1 agonist capsaicin (CAP; 1–100 μg/kg). Arterial pressures (AP) and heart rate (HR) were simultaneously recordedfor double product (DP) measurement as a surrogate of myocardial oxygen consumption. In controls, CAP produced a dose‐dependent increase in MBF, which was significantly blunted in db/db mice, despite db/db having a higher DP. Low pH changes induced vasodilation in isolated mesenteric microvessels from controls, which was blunted in microvessels from db/db, TRPV1 −/− and control after TRPV1 inhibition (SB366791), suggesting a portion of low pH induced vasodilation may be due to TRPV1 activation. We conclude that TRPV1 channels may be involved in the metabolic regulation of myocardial blood flow and this mechanism appears to be corrupted in diabetic mice.