Coronary Microvascular Function and Beyond: The Crosstalk between Hormones, Cytokines, and Neurotransmitters

Figure 1

Physical, metabolic, and neural factors modulate microvascular coronary blood flow [9]. The coronary blood flow (CBF) is driven by the pressure difference between the aortic sinus and the coronary sinus (or the right atrium pressure). In the absence of obstructive stenoses, the epicardial arteries offer very little (10%) resistance to CBF and serve mainly as conductance vessels. Capillaries and venules are likewise responsible for only 10% of CBF resistance and mainly function as capacitance vessels, holding 90% of the total myocardial blood volume. Under normal conditions and to a large extent also under pathological conditions, coronary vascular resistance is primarily controlled by the prearterioles (vessels of 500 mm in diameter) and arterioles (200 mm). The prearterioles are epicardial (extramyocardial) vessels that react to changes in shear stress and intravascular pressure to preserve adequate perfusion pressure in the distal arteriolar bed. They are responsible for 25% of the total coronary vascular resistance. The arterioles are the true intramyocardial regulatory component of the coronary circulation and these vessels represent the largest proportion (55%) of the total coronary vascular resistance. Endothelium-dependent vasoreactivity prevails in the larger arterioles (100–200 mm in diameter) and translates flow-related stimuli into vasomotor responses, that is, vasodilation with increase in flow and vice versa. Medium-sized microvessels (40–100 mm in diameter) react predominantly to intraluminal pressure changes sensed by stretch receptors located in vascular smooth muscle cells (myogenic control, through signals mediated by phospholipase C and protein kinase C and calcium homeostasis); that is, they constrict when the intraluminal pressure increases and, conversely, dilate when the pressure decreases. Finally, the tone of the smaller arterioles (vessels of 40 mm in diameter) is modulated by the metabolic activity of the myocardium. As such, increased metabolic activity leads to vasodilatation of the smaller arterioles, which leads to pressure reduction in the medium-sized microvessels and myogenic dilation, which, in turn, increases flow upstream resulting in endothelium-dependent vasodilation. These mechanisms effectively and efficiently allow the microcirculation to regulate myocardial perfusion both at rest and at different levels of myocardial metabolic demand. LVEDP: left ventricular end diastolic pressure; RVED: right ventricular end diastolic pressure; ET-1: endothelin-1; ANG II: angiotensin II; NO: nitric oxide; EDHF: endothelial derived factor; PLC: phospholipase C; PKC: protein kinase C (modified from [9]).