Izzard Ashley S, Heagerty Anthony M
Institute of Cardiovascular Sciences, Core Technology Facility (3rd Floor), University of Manchester, Manchester M13 9NT, UK.
Curr Vasc Pharmacol. 2014;12(6):829-35. doi: 10.2174/15701611113116660150.
Intrinsic arterial myogenic function comprises the degree of constriction (myogenic tone), the arterial constriction to an increase in intraluminal pressure and vice versa (myogenic response), and forced dilation at high intraluminal pressure. Although the development of myogenic tone at 40-60 mmHg involves the influx of calcium (Ca(2+)) through voltage- dependent Ca(2+) channels and an elevation in arterial intracellular Ca(2+) (Ca(2+) i), myogenic responses between 60-140 mmHg involves predominantly Rho kinase (ROK)-mediated changes in Ca(2+) sensitivity. In the cerebral circulation an impaired myogenic response results in impaired cerebral autoregulation and susceptibility hypertension-induced cerebral haemorrhage. An impaired cerebral artery myogenic response, due to blunted ROK mediated changes in Ca(2+) sensitivity, may be a consequence of defective mechanotransduction of the intraluminal pressure stimulus; this may be a result of abnormalities in the extracellular matrix. In the coronary circulation distinctions between the mechanisms involved in the development of myogenic tone and the myogenic response have not been clearly defined. However, coronary artery myogenic tone is dependent on both Ca(2+) entry through voltage -dependent Ca(2+) channels and protein kinase C (PKC) activity. Impaired coronary myogenic tone has been observed in animal models of disease but the implications of these findings are currently uncertain.
动脉内在肌源性功能包括收缩程度(肌源性张力)、管腔内压力升高时的动脉收缩以及相反情况(肌源性反应),以及在高管腔内压力下的强制扩张。虽然在40 - 60 mmHg时肌源性张力的产生涉及钙(Ca(2+))通过电压依赖性Ca(2+)通道的内流以及动脉细胞内Ca(2+)(Ca(2+)i)的升高,但在60 - 140 mmHg之间的肌源性反应主要涉及Rho激酶(ROK)介导的Ca(2+)敏感性变化。在脑循环中,受损的肌源性反应会导致脑自动调节功能受损以及高血压诱导的脑出血易感性增加。由于ROK介导的Ca(2+)敏感性变化减弱,脑动脉肌源性反应受损可能是管腔内压力刺激机械转导缺陷的结果;这可能是细胞外基质异常的结果。在冠状动脉循环中,肌源性张力产生机制与肌源性反应机制之间的区别尚未明确界定。然而,冠状动脉肌源性张力依赖于通过电压依赖性Ca(2+)通道的Ca(2+)内流和蛋白激酶C(PKC)活性。在疾病动物模型中已观察到冠状动脉肌源性张力受损,但这些发现的意义目前尚不确定。