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Contribution of Voltage‐Dependent Potassium & Calcium Channels to Coronary Pressure‐Flow Autoregulation
Author(s) -
Berwick Zachary C,
Moberly Steven P,
Kohr Meredith C,
Morrical Ethan B,
Kurian Michelle M,
Goodwill Adam G,
Tune Johnathan D
Publication year - 2012
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.26.1_supplement.1055.12
Subject(s) - diltiazem , autoregulation , vasodilation , coronary perfusion pressure , medicine , cardiology , perfusion , coronary circulation , chemistry , blood pressure , blood flow , potassium channel , calcium , hemodynamics , anesthesia , cardiopulmonary resuscitation , resuscitation
The goal of this investigation was to test the hypothesis that voltage‐sensitive potassium (K V ) and calcium (Ca V 1.2) channels contribute to coronary pressure‐flow autoregulation in vivo . This hypothesis was tested in open‐chest, anaesthetized Ossabaw swine during step changes in coronary perfusion pressure (CPP) from 140‐40 mmHg before/during inhibition of K V channels with 4AP (0.3 mM, ic) or Ca V 1.2 channels with diltiazem (10 μg/min, ic). 4AP significantly decreased vasodilatory responses to H 2 O 2 (0.3 – 10 μg/min) and blood flow at CPPs = 140‐60 mmHg. This decrease in coronary flow was associated with diminished ventricular contractile function (dP/dT) and myocardial oxygen consumption. However, the overall sensitivity to changes in CPP from 120 to 60 mmHg (i.e. autoregulatory gain; Gc) was unaltered by 4‐AP administration (Gc = 0.35 ± 0.11 control vs. 0.39 ± 0.07 4‐AP). In contrast, diltiazem markedly increased coronary blood flow at CPPs > 80 mmHg and decreased coronary autoregulatory gain (Gc = −0.21 ± 0.08) relative to control ( P < 0.01), with no effect on contractile function or oxygen consumption. Taken together, our findings demonstrate that: 1) K V channels tonically contribute to the control of vascular resistance over a wide range of CPPs; 2) Ca V 1.2 channels play a critical role in coronary pressure‐flow autoregulation.