F7v: Describe the role of endogenous nitric oxide in ventilation and perfusion

Nitric oxide

Produced by endothelial cells to relax vascular smooth muscle and cause vasodilation
Formed from L arginine via endothelial NO synthase

Shear stress neurotransmitters (bradykinin, substance P, histamine), metabolic activity (Increase H, K, PaCO2, adenosine, temperature, lactate, decrease PaO2), volatiles

Diffuses into vascular smooth muscle -> NO stimulates guanalyl cyclase -> increase cGMP -> activates protein kinase G -> inhibits IP3 mediated release of calcium -> decrease intracellular calcium
- SM: relaxation -> vasodilation
- Lung: pulmonary vasodilation -> improves VQ mismatch, decrease pulmonary vascular resistance, decrease pulmonary artery pressure
  - More details below

Largest impact on hypoxic pulmonary vasoconstriction
- eNO decreases HPV
- Therefore dilates pulmonary vessels which are well ventilated to allow increased perfusion
- Overall reduces intrapulmonary shunt -> improves VQ matching and increases arterial oxygenation
Other perfusion related:
- Increases HR by stimulating the hyperpolarisation-activated Inward Current
- Increase cardiac contractility
  - The efficiency of myocardial contractility is ideal – therefore interestingly decreases myocardial oxygen consumption
- Decrease right ventricular pressure, decrease intracardiac shunt, increase right ventricular ejection fraction

Decrease PVR, PAP
- Relationship between PVR and lung volume is U shaped
- PVR is lowest at FRC
- Therefore decreasing PVR to as close as possible to FRC will allow for benefits including: decrease work of breathing, small airway resistance is low (prevents atelectasis/gas trapping), maximal lung compliance
Increase bronchial dilation
- Areas of well ventilated lungs are more likely to receive increased perfusion (in the presence of iNO and HPV mechanism is intact)
  - Overall improves VQ mismatch

Author: Suzanne Luong