Contribution of voltage-dependent K+ and Ca2+ channels to coronary pressure-flow autoregulation.
Contribution of voltage-dependent K+ and Ca2+ channels to coronary pressure-flow autoregulation.
复制标题
电压依赖性K+和Ca2+通道对冠状动脉自动调节的贡献。
DOI：
10.1007/s00395-012-0264-6
复制
发表时间：
2012-05
影响因子：
9.5
通讯作者：
Tune JD
中科院分区：
文献类型：
--
作者：
Berwick ZC;Moberly SP;Kohr MC;Morrical EB;Kurian MM;Dick GM;Tune JD
冠状动脉压力-血流自动调节是在灌注压力变化时维持冠状动脉血流相对恒定的一种关键生理现象，但其机制尚不清楚。本研究验证了电压敏感的K+ (KV)和Ca2+ (CaV1.2)通道在体内冠状动脉压力-血流自动调节中起关键作用的假设。在4-氨基吡啶（4AP, 0.3 mM, ic）和地尔硫卓（10 μg/min, ic）抑制KV通道前和抑制KV通道期间，开胸麻醉的奥沙巴猪冠状动脉灌注压（CPP）从40 ~ 140 mmHg逐步变化。4AP显著降低H2O2 （0.3-10 μM, ic）对血管的舒张反应和cps = 60-140 mmHg时的冠状动脉血流。冠状动脉血流的减少与心室收缩功能（dP/dT）和心肌耗氧量的降低有关。然而，4-AP对CPP从60到100 mmHg变化的总体敏感性（即自动调节增益；Gc）没有改变（对照Gc = 0.46±0.11 vs. 0.46±0.06 4-AP）。相比之下，抑制CaV1.2通道可使冠脉血流量在CPPs bbb80 mmHg时逐渐增加，并使冠脉Gc显著降低至- 0.20±0.11 (P < 0.01)，但对收缩功能和耗氧量没有影响。综上所述，这些发现表明：(1)KV通道在很大范围内有助于控制微血管阻力，但不影响冠状动脉对压力变化的反应；(2)随着CPP的增加，CaV1.2通道的逐渐激活是冠状动脉压力-血流自动调节的关键机制。
The mechanisms responsible for coronary pressure-flow autoregulation, a critical physiologic phenomenon that maintains coronary blood flow relatively constant in the presence of changes in perfusion pressure, remain poorly understood. This investigation tested the hypothesis that voltage-sensitive K+ (KV) and Ca2+ (CaV1.2) channels play a critical role in coronary pressure-flow autoregulation in vivo. Experiments were performed in open-chest, anesthetized Ossabaw swine during step changes in coronary perfusion pressure (CPP) from 40 to 140 mmHg before and during inhibition of KV channels with 4-aminopyridine (4AP, 0.3 mM, ic) or CaV1.2 channels with diltiazem (10 μg/min, ic). 4AP significantly decreased vasodilatory responses to H2O2 (0.3–10 μM, ic) and coronary flow at CPPs = 60–140 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 60 to 100 mmHg (i.e. autoregulatory gain; Gc) was unaltered by 4-AP administration (Gc = 0.46 ± 0.11 control vs. 0.46 ± 0.06 4-AP). In contrast, inhibition of CaV1.2 channels progressively increased coronary blood flow at CPPs > 80 mmHg and substantially diminished coronary Gc to −0.20 ± 0.11 (P < 0.01), with no effect on contractile function or oxygen consumption. Taken together, these findings demonstrate that (1) KV channels tonically contribute to the control of microvascular resistance over a wide range of CPPs, but do not contribute to coronary responses to changes in pressure; (2) progressive activation of CaV1.2 channels with increases in CPP represents a critical mechanism of coronary pressure-flow autoregulation.
登录
查看更多内容
影响因子：
3.3
作者：
Heaps, Cristine L.;Jeffery, Elise C.;Bowles, Douglas K.
通讯作者：
Bowles, Douglas K.
影响因子：
9.5
作者：
DEFILY, DV;CHILIAN, WM
通讯作者：
CHILIAN, WM
影响因子：
20.1
作者：
DRISCOL, TE;MOIR, TW;ECKSTEIN, RW
通讯作者：
ECKSTEIN, RW
影响因子：
2.4
作者：
Berwick, Zachary C.;Payne, Gregory A.;Tune, Johnathan D.
通讯作者：
Tune, Johnathan D.
DOI：
10.1152/ajpheart.00888.2009
发表时间：
2010-04-01
影响因子：
4.8
作者：
Borbouse, Lena;Dick, Gregory M.;Tune, Johnathan D.
通讯作者：
Tune, Johnathan D.