Changes of Vascular Architecture Independent of Blood Pressure in Experimental Uremia

Striking alterations of the structure of arterial vessels of different caliber are a well-known feature of renal failure, but it is currently unknown to what extent they are a reflection of hypertension or of uremia per se. To address this issue further we studied subtotally nephrectomized rats, sham-operated and pair-fed with matched controls. After uremia of 14 daysʹ duration, stereologic measurements were carried out on perfusion-fixed tissue. To eliminate a potential influence of hypertension, subgroups of animals received furosemide and hydralazine in the drinking fluid to yield daily doses of 15 mg/kg and 20 mg/kg, respectively. At the end of the experiment, systolic blood pressure (tail plethysmography) was 110 ± 13.3 (mean ± SD) mm Hg and 99.4 ± 8.1 mm Hg in untreated and treated controls, respectively, and 132 ± 20.7 mm Hg and 103 ± 13.0 mm Hg in untreated and treated uremic animals, respectively (n = 5 to 10 animals per group). The wall:lumen ratio of intramyocardial small arteries was 0.056 ± 0.011 and 0.052 ± 0.006 in untreated and treated controls, respectively. In untreated and treated uremic animals, the corresponding values were 0.077 ± 0.011 and 0.066 ± 0.007 (P< .01; control v uremia, ANOVA). A similar increase, unaffected by blood pressure treatment, was found for wall thickness of intramyocardial arteries. Analogous changes were also noted in mesenteric arterioles and veins. Finally, aorta media thickness was significantly (P< .005) higher in uremic animals than in controls (138 ± 29 μm v 103 ± 14 μm). Additionally, aortic media and lamina elastica interna showed significant architectural abnormalities. The results document pressure-independent structural alterations in arterial (resistance and Windkessel) as well as venous vessels of uremic animals. The changes are of potential importance for resistance and impedance in renal failure.