Effects of hypoxia on renal hormonal balance in normal subjects and in patients with COPD

Abstract

There is a complex interaction between pulmonary haemodynamics, hormonal, and salt and water balance in patients with chronic obstructive pulmonary disease (COPD) and in normal subjects exposed to hypoxia or high altitude. This study aims to investigate the effects of hypoxia on renal hormonal balance in normal subjects and patients with COPD, particularly the role of urinary dopamine and atrial natriuretic peptide (ANP). Urinary dopamine output, ANP, and plasma renin activity (PRA) were measured in 12 normal subjects exposed to hypoxia (12% O2) and hyperoxia (40% O2) for 1 h and in 15 patients with exacerbations of COPD while breathing air or O2. These measurements were repeated in six of the patients with exacerbations of COPD when they were clinically stable. Hypoxia caused an increase in ANP levels (49 +/- 6-62 +/- 6 pg ml-1, P < 0.05) and a fall in urinary dopamine output (277 +/- 39-205 +/- 33 ng h-1, P < 0.002) in normal subjects. Hyperoxia was associated with a return of plasma ANP to the baseline values. In patients with exacerbations of COPD plasma ANP levels were higher (181 +/- 36 pg ml-1) than in normal subjects (49.5 +/- 6.5 pg ml-1, P < 0.001). Urinary dopamine output breathing air (175 +/- 34 ng h-1) was similar to the levels when normal subjects were made hypoxaemic and PRA was elevated in comparison to normal values. There was no change in their levels following the acute administration of oxygen in patients presenting with exacerbations of COPD, but oxygen improved urinary sodium excretion (P < 0.05). In six patients re-studied when clinically stable there was a fall in urinary dopamine output, plasma ANP and PRA when breathing air in comparison to the acute stage of the disease (P < 0.05). These data suggest presence of renal hormonal imbalance including endogenous urinary dopamine output during hypoxic exacerbation of COPD and in normal subjects exposed to hypoxia.

Fluid homeostasis in chronic obstructive lung disease

“…Other studies that have looked into urinary sodium excretion in patients with COPD and normal controls [21,22] can be criticised on similar grounds or because medication (diuretics) could not be eliminated for a sufficiently long period of time or because the observation period was too short. Nevertheless, studies in normal subjects who also respond to acute hypoxia with a reduction in sodium output [22,23] support the notion that a fall in Pa,O 2 is associated with enhanced retention of sodium.…”

“…Hypoxia and hypercapnia are also associated with increased levels of renin [15,23,[39][40][41]. This has often been attributed to the decline in renal perfusion but again this may be too simplistic an explanation because patients with essential hypertension often have low levels of renin in conjunction with impaired renal blood flow [36,42].…”

Cardiovascular Injury and Repair in Chronic Obstructive Pulmonary Disease

“…These effects of acute and intermittent hypoxia may have relevance for individuals with COPD, who are subjected to intermittent hypoxic episodes during exertion and exacerbations. Hypoxia also affects the renal circulation, reducing renal blood flow and activating the renin angiotensin system, resulting in increased peripheral vasoconstriction and oxidative stress (64).…”

Underlying Mechanisms of Cardiovascular Disease in Chronic Obstructive Pulmonary Disease

“…In normal subjects, a hypoxic challenge increases heart rate and cardiac index. Hypoxia also reduces renal blood flow and activates the renin-angiotensin system, with consequent increased peripheral vasoconstriction and oxidative stress 50 .…”