Hypoxic Pulmonary Vasoconstriction

Hypoxic pulmonary vasoconstriction (HPV) is the lung's distinctive response in which a fall in alveolar oxygen tension constricts the small pulmonary arteries supplying that region. By diverting blood away from poorly ventilated areas toward better-ventilated ones, it acts to match perfusion to ventilation and so preserve the oxygenation of the blood leaving the lung.

Definition

Hypoxic pulmonary vasoconstriction is the active contraction of pulmonary arterial smooth muscle in response to low alveolar (and to a lesser extent mixed venous) oxygen tension, a response unique to the pulmonary circulation in that hypoxia constricts rather than dilates these vessels.

Scope

The entry covers the phenomenon of HPV, its role in matching perfusion to ventilation, the cellular oxygen-sensing and signalling mechanisms thought to underlie it, and the systemic consequences of generalized hypoxia such as that at altitude. It is a reference physiology topic and explains mechanisms; it does not give clinical or treatment guidance.

Core questions

• What stimulus triggers hypoxic pulmonary vasoconstriction?
• How does it improve the matching of perfusion to ventilation?
• How do pulmonary arterial smooth-muscle cells sense oxygen and transduce the signal to contraction?
• What happens when hypoxia is global rather than local, such as at high altitude?

Key concepts

• Alveolar hypoxia as the stimulus
• Ventilation-perfusion matching
• Pulmonary arterial smooth-muscle oxygen sensing
• Reactive oxygen species and redox signalling
• Potassium-channel inhibition and membrane depolarization
• Calcium entry and sensitization
• Global hypoxia and pulmonary hypertension

Mechanisms

When alveolar oxygen falls, the small pulmonary arteries supplying that alveolus constrict, so blood is redirected toward better-oxygenated regions and overall gas exchange is protected (Sylvester et al., 2012). The response is intrinsic to the pulmonary arterial smooth-muscle cell: the prevailing model holds that the cell senses oxygen through mitochondrial and redox signalling, that the resulting change in reactive oxygen species inhibits voltage-gated potassium channels, and that the consequent depolarization opens voltage-gated calcium channels; rising intracellular calcium, together with calcium sensitization of the contractile apparatus, produces contraction (Sommer et al., 2008; Sommer et al., 2016). When hypoxia affects the whole lung—at altitude or in chronic lung disease—the response becomes generalized, raising pulmonary arterial pressure and, if sustained, contributing to vascular remodelling (Sylvester et al., 2012; Suresh & Shimoda, 2016).

Clinical relevance

Hypoxic pulmonary vasoconstriction is a normal regulatory mechanism whose generalized form underlies the rise in pulmonary pressure seen with sustained whole-lung hypoxia. This entry describes the physiology and its mechanisms; it is educational and is not a basis for diagnosing, monitoring, or treating any individual.

Evidence & guidelines

Understanding of HPV rests on extensive experimental work synthesized in major reviews. The Physiological Reviews monograph remains the most comprehensive account of the phenomenon and its proposed mechanisms (Sylvester et al., 2012), and dedicated reviews detail the oxygen-sensing and signal-transduction steps in pulmonary arterial smooth muscle (Sommer et al., 2008; Sommer et al., 2016).

History

That alveolar hypoxia constricts the pulmonary vessels was established in the mid-twentieth century—classically attributed to the observations of von Euler and Liljestrand—and was recognized as the opposite of the systemic vasculature's response to hypoxia. Decades of subsequent work, summarized in comprehensive reviews, have sought to identify the oxygen sensor and the signalling chain linking it to smooth-muscle contraction (Sylvester et al., 2012; Sommer et al., 2008).

Debates

What is the oxygen sensor underlying HPV?

Whether the proximate sensor is the mitochondrion acting through reactive oxygen species, an NADPH-oxidase, or another redox system—and how its output is coupled to potassium-channel inhibition—remains unsettled and is reviewed as an open question.

Key figures

• J. T. Sylvester
• Norbert Weissmann
• Larissa A. Shimoda

Seminal works

• sylvester-2012
• sommer-2008

Frequently asked questions

Why does the lung constrict its vessels in response to low oxygen when other organs dilate theirs?

In the lung, constricting vessels in a poorly oxygenated region diverts blood toward better-ventilated areas, which improves gas exchange; in systemic organs, dilation in response to low oxygen instead increases local blood supply. The pulmonary response serves perfusion-ventilation matching rather than local delivery.

What happens to hypoxic pulmonary vasoconstriction at high altitude?

Because the entire lung is hypoxic, the response becomes generalized rather than regional, raising pulmonary arterial pressure overall; sustained global hypoxia can therefore contribute to pulmonary hypertension.