The effects of chronic hypoxia on renal function in the rat

Abstract

Studies were performed on rats that had been made chronically hypoxic (CH rats) in a normoxic chamber at 12% O2 for 3–5 weeks. Under Saffan anaesthesia, respiratory and cardiovascular variables, renal haemodynamics and renal function were recorded while the rats spontaneously breathed 12% O2 followed by a switch to air breathing for 20 min. Plasma renin activity was assessed by radioimmunoassay of angiotensin I. Plasma atrial natiruetic peptide (ANP) was indirectly assessed by measurement of cyclic GMP in urine. When breathing 12% O2, CH rats showed hyperventilation and raised haematocrit (52%) relative to normoxic (N) rats. But arterial pressure (ABP), renal blood flow (RBF), renal vascular conductance (RVC), mean right atrial pressure (mRAtP), urine flow, glomerular filtration rate (GFR) and absolute sodium excretion (UNaV) were comparable to those recorded in N rats breathing air. Urinary cGMP was 40% greater than in N rats, but plasma renin activity was not significantly greater in CH than in N rats. Air breathing in CH rats induced hypoventilation, a 12% increase in ABP, no change in mRAtP, RBF or GFR, but increases of 75 and 100% in urine flow and UNaV, respectively. Neither urinary cGMP nor plasma renin activity changed. Such increases in urine flow and UNaV were absent when renal perfusion pressure (RPP) was prevented from rising during air breathing by using an occluder on the dorsal aorta. We propose that by 3–5 weeks of chronic hypoxia renal function was normalized, principally because arterial O2 content was normalized by the increase in haematocrit and because ABP and renal haemodynamics were normalized: acute hypoxia in N rats produces a fall in ABP. We suggest that plasma ANP was raised by the actions of hypoxia or erythropoietin on the atrium, rather than by atrial distension, but suggest that ANP had little direct influence on renal function and tended to limit the influence of the renin–angotensin system. We further propose that the diuresis and natriuresis seen during air breathing were mediated by the increase in RPP; neither plasma ANP nor renin activity change in the immediate short term.

Chronic intermittent hypercapnic hypoxia increases pulmonary arterial pressure and haematocrit in rats

“…Similarly, in rats, diuresis and natriuresis [36] or antidiuresis and antinatriuresis [37] have been described. However, more recent evidence suggests that acute hypoxia in rats causes antidiuresis and antinatriuresis [38,39] and that chronic hypoxia results in normal renal function [40]. Therefore, it is believed that a decrease in plasma volume is an unlikely contributor to the increased haematocrit in the present experiments.…”

Hypoxia and high glucose upregulate AT1receptor expression and potentiate ANG II-induced proliferation in VSM cells

“…2), indicating a stimulating effect of hypoxia on both AT 1 expression and receptor density in VSM cells. Chronic systemic hypoxia has been shown to activate RAS in a number of tissues, including the kidney, lung, heart, and pancreas (11,29,34). Leung et al (24) also recently reported an upregulation of AT 1 receptor expression and function in the carotid body by isobaric hypoxia.…”

Quantitative studies of the vasculature of the carotid body in the chronically hypoxic rat

“…In another investigation (18) concerning the effect of sympathectomy on long-term hypoxic rats, the authors gave insufficient information on their methods to allow us to comment on their findings of different sizes of blood vessels within the organ. We emphasise that the changes observed in the two compartments of the carotid body in our experiments occurred in the absence of an increase in venous pressure in vivo (19) and that during the perfusion-fixation procedure we used, retrograde filling and artificial distension of the organs venous microvasculature after death were prevented by raising the animals head just above the level of the thorax.…”