Acute hypoxia and pulmonary vasoconstriction in humans: uncovering the mechanism of the pressor response

Abstract

This essay looks at the historical significance of an APS classic paper that is freely available online:Motley HL, Cournand A, Werko L, Himmelstein A, and Dresdale D. The influence of short periods of induced acute anoxia upon pulmonary artery pressures in man. Am J Physiol 150: 315-320, 1947 (http://ajplegacy.physiology.org/cgi/ reprint/150/2/315).FOR THE LUNGS TO OPERATE EFFICIENTLY in gas exchange, it is essential for the pulmonary blood flow to be directed to well-ventilated areas of the lungs. Teleologically, one mechanism to accomplish this end might be via nerves and pulmonary reflexogenic zones comparable to the sinus and aortic bodies in the systemic circulation. Although the lungs are richly innervated, no evidence indicates that such zones exist or that the nerves to the lungs play such a role. Instead, a mechanism for the control of the distribution of blood within the lungs is hypoxic pulmonary vasoconstriction, which automatically increases pulmonary vascular resistance in poorly aerated regions of the lungs, thereby redirecting pulmonary blood flow to regions richer in oxygen content.A first step in uncovering the existence of hypoxic pulmonary vasoconstriction was taken by Euler and Liljestrand (6, 10). In closed-chest, spontaneously breathing cats anesthetized with chloralose, they showed that acute hypoxia elicits pulmonary vasoconstriction (Fig. 2). They postulated that hypoxic pulmonary vasoconstriction is a mechanism that sustains oxygen delivery to systemic tissues and organs by diverting pulmonary blood flow to the better aerated parts of the lungs. This demonstration, which they supplemented by observations on the effects of muscular work and vasoactive drugs on pulmonary arterial pressures, led to the conclusion that the distribution of the pulmonary blood flow within the lungs is regulated primarily by a local vasomotor mechanism that automatically directs the blood to better ventilated parts of the lungs.Motley et al. (13), in the laboratory of André Cournand (Fig. 1) at Bellevue Hospital, aware of the recent observations by Euler and Liljestrand on anesthetized cats, undertook similar observations on five normal human subjects. The subjects were rendered hypoxic by breathing an inspired gas mixture of 10% O 2 in N 2 for 10 min. In each subject, acute hypoxia elicited pulmonary vasoconstriction, as indicated by an increase in pulmonary arterial pressure. The demonstration of the hypoxic pulmonary pressor response in unanesthetized humans breathing spontaneously represented a landmark in the growth of understanding of the regulation of pulmonary circulation.Unexpectedly, they found that the pulmonary arterial pressor effect was accompanied by a decrease in cardiac output, which they calculated by the Fick principle. However, this decrease in calculated cardiac output during acute hypoxia proved later to be in error (8), due to failure to allow sufficient time for the subjects to reach the steady state of the respiration and circulation required for a valid application of the Fick prin...

Elevated pulmonary artery pressure among Amhara highlanders in Ethiopia

“…At high altitude, the entire lung is unavoidably exposed to lowered inspired oxygen. An immediate reaction is the hypoxic pulmonary vasoconstriction reflex, measured as an increase in pulmonary artery blood pressure, that “automatically increases pulmonary vascular resistance in poorly aerated regions of the lungs, thereby redirecting pulmonary blood flow to regions richer in oxygen content” (Fishman,2004 p. L893). Lifelong exposure would predict unrelieved hypoxic pulmonary vasoconstriction and lead to sustained elevated pulmonary artery pressure and vascular resistance that could progress to cardiac enlargement (cor pulmonale) or right heart failure.…”

Reflexes from pulmonary arterial baroreceptors in dogs: interaction with carotid sinus baroreceptors

“…The pulmonary baroreceptors may also be of importance during exposure to hypoxic stress. For example, pulmonary hypertension is known to develop in unacclimatized healthy individuals exposed to high altitude; this is due to vasoconstriction of small muscular resistance pulmonary arteries in response to alveolar hypoxia (Fishman, 2004). In contrast, systemic blood pressure at high altitude is slightly lower than it is a sea level.…”

Elevated Blood Pressure of High Altitude Dwelling Andibila Adults in Oju, Nigeria

“…The increase in systematic arterial pressure during acute exposure to high altitude, and the accompanying changes in blood pressure have been linked to increase in autonomic and sympathetic activity (Rhodes et al, 2011). The exposure of the lung at high altitude decreases inspired oxygen, thereby triggering hypoxic pulmonary vasoconstriction reflex (Fishman, 2004). Prolonged exposure hypoxia might result to sustain elevated arterial BP and diastolic BP (Hoit, Dalton, Gebremedin, Janocha, Zimmerman, & Zimmerman, 2011;Wolfel, Selland, Mazzeo, & Reeves, 1994).…”

“…Prolonged exposure hypoxia might result to sustain elevated arterial BP and diastolic BP (Hoit, Dalton, Gebremedin, Janocha, Zimmerman, & Zimmerman, 2011;Wolfel, Selland, Mazzeo, & Reeves, 1994). However, arterial BP remains normal by enhanced vascularization attributable to decreased total peripheral resistance in adults residing in mountainous regions (Fishman, 2004;Pocock & Richards, 1999). Again, other studies have reported that inhabitants of high altitude exhibits lower systolic and diastolic BP readings compared to low altitude population (Hoit, Dalton, Gebremedin, Janocha, Zimmerman, & Zimmerman, 2011;Hanna, 1999;Shrestha, Shrestha, Shrestha, & Bhattarai, 2012;Tripathy & Gupta, 2007).…”