Hypoxic Pulmonary Vasoconstriction

In the fetus, partially oxygenated blood returning from the placenta, flows through the right side of the heart. Because of the high resistance of the unexpanded lungs, the blood is diverted from the right atrium and pulmonary artery, across the foramen ovale and ductus arteriosus to the left atrium and aorta respectively. The high pulmonary vascular resistance (PVR) in utero can be demonstrated to be due in part to hypoxic pulmonary vasoconstriction (HPV), as when a maternal animal is ventilated with high concentrations of oxygen, the fetal PVR falls. At birth as the oxygen tension rises, the small, resistance pulmonary arteries dilate and the ductus arteriosus contracts. The opposite response of these vessels to the increase in oxygen is a fascinating conundrum.

After birth, HPV may occur as a result of a localized area of alveolar hypoventilation (e.g., atelectasis). This HPV diverts the flow of relatively desaturated, mixed venous blood to better ventilated areas of the lung. If HPV is inhibited, there is a reduction in systemic arterial oxygen tension, even in normal subjects, but particularly in patients with small airways disease [7]. Thus HPV in the presence of localized hypoxia is beneficial but generalized hypoxia can lead to pulmonary hypertension and remodeling. Acute HPV predominantly affects small pulmonary arteries and veins (< 500 | in diameter) [23]. The "executive" mechanism of HPV has three components. The first requires hypoxic inhibition of K+ channels in the cell membrane of the pulmonary artery smooth muscle cells (PASMCs), membrane depolarization and calcium entry through the L-type calcium channel, just as occurs in the carotid body type 1 cell [18] [13]. The second involves release of calcium from the sarcoplasmic reticulum of PASMCs into the cytoplasm and its repletion by calcium entry through store-operated calcium (SOC) channels [21] [27]. The third mechanism exploits calcium sensitization [20], which can sustain smooth muscle contraction when cytosolic levels of calcium are decreasing [25]. Myosin light-chain phosphatase normally dephosphorylates myosin light-chain and ends the interaction between actin and myosin that is responsible for calcium-calmodulin mediated smooth muscle contraction. During hypoxia there is an increase in the activated form of the small G protein, RhoA, in PASMCs. Active RhoA stimulates Rho kinase which then inhibits myosin light-chain phosphatase and prevents dephosphoryla-tion, thus prolonging and augmenting HPV. In the presence of localized areas of acute alveolar hypoxia these three mechanisms result in localized HPV.

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Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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