Microvascular and tubulointerstitial injury associated with chronic hypoxia-induced hypertension.
BACKGROUND
Rats submitted to chronic hypoxia develop hypertension that persists despite cessation of the hypoxia or correction of the hematocrit. We examined whether chronic hypoxia might induce subtle renal injury since studies in other animal models of hypertension suggest this may cause persistent hypertension.


METHODS
Chronic hypoxia was induced in rats by placement in a hypobaric chamber for up to 24 days. Blood pressure and kidney biopsies were performed at baseline, 6 hours, 24 hours, and 24 days of hypoxia.


RESULTS
Chronic hypoxia induced hypertension and erythrocytosis at 24 days. Acute hypoxia was associated with endothelial cell swelling in arterioles (6 and 24 hours), followed by thickening of the arterioles at 24 days. Subtle tubulointerstitial injury and inflammation occurred and was progressive. The influx of macrophages increased steadily over the 24 days and was associated with a progressive increase in interstitial collagen III deposition. Hypoxia was associated with increased tubular expression of osteopontin as early as 6 hours, the same period when an increase of proximal tubular cell proliferation occurred. Interstitial cell proliferation peaked twice, at 6 hours and at 24 days. Glomerular hypertrophy was manifest at 24 days.


CONCLUSIONS
Both afferent arteriolar disease and subtle tubulointerstitial inflammation and injury occur early in hypoxic rats. These changes may predispose these animals to persistent hypertension.
Mazzali
Marilda
M
Division of Nephrology, Baylor College of Medicine, Houston, Texas 77030, USA.
Jefferson
J Ashley
JA
Ni
Zehmin
Z
Vaziri
Nosratola D
ND
Johnson
Richard J
RJ
D000818:Animals; D002455:Cell Division; D002908:Chronic Disease; D005921:Glomerulonephritis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D006977:Hypertension, Renal / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D033461:Hyperuricemia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D008833:Microcirculation; D011086:Polycythemia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation