Influence of different stages of experimental chronic kidney disease on rats locomotor and postural skeletal muscles microcirculation.
BACKGROUND
Chronic kidney disease (CKD) is associated with muscle excess fatigue and diminished maximal whole body oxygen consumption, which in part could be depended on poor muscle microcirculatory network. The aim of this study was to assume the influence of different stages of CKD on microcirculation vessels in functionally different skeletal muscles--locomotor, the gastrocnemius muscle, and postural, the longissimus thoracis muscle.


METHODS
Male Wistar rats underwent sham operation (CON), uninephrectomy (CKD 1/2) and subtotal nephrectomy (CKD 5/6). Muscle samples were stained for an alkaline phosphatase to differentiate capillaries. The number of capillaries was estimated by a single observer in 10 microm transverse sections by point counting at a magnification of x 125 using an Image Analysis System Q 500 MC of Leica. Blood pressure and serum creatinine, haptoglobin, MCP-1, VEGF, and PDGF were measured.


RESULTS
There were significant differences (p < 0.05) in CD (number of capillaries per 1 mm(2) of muscle tissue), C:F (capillary to fiber ratio), and CC/F (capillary contact per fiber). The CKD 1/2 group in gastrocnemius and longissimus muscle had 53% and 33% lower C:F; 56% and 33% lower CD; and 44% and 20% less CC/F than CON, respectively. The CKD 5/6 group in gastrocnemius and longissimus muscle had 46% and 20% lower C:F; 47% and 11% lower CD; and 48% and 25% less CC/F versus control, respectively. Blood pressure was higher in CKD 5/6 vs. CKD 1/2 and CON (145/95 vs. 107/87 and 119/77 mmHg, p < 0.05, respectively). CKD 5/6 had higher creatinine than CKD 1/2 and CON (1.22 vs. 0.83 and 0.74 mg/dL, p < 0.05, respectively). Haptoglobin was higher in CKD 1/2 and CKD 5/6 versus CON (1.68 and 1.63 vs. 0.70 mg/mL, p < 0.05, respectively). MCP-1 was higher in CKD 5/6 and CKD 1/2 versus CON (609 and 489 vs. 292 pg/mL, p < 0.05, respectively). There were no significant differences in serum growth factors concentration between groups.


CONCLUSIONS
Capillary rarefaction is present in early stages of CKD. These changes are independent of blood pressure and progression of CKD. We suspected that muscle function has a big impact on microvasculature as capillaries rarefaction has been reduced more in locomotor than postural skeletal muscle.
Department of Nephrology, Hypertension and Internal Diseases of Ludwig Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland. nerka@nerka.cpro.pl
Mariusz
M
Flisiński
Andrzej
A
Brymora
Gabriela
G
Elminowska-Wenda
Joanna
J
Bogucka
Konrad
K
Walasik
Anna
A
Stefańska
Grazyna
G
Odrowaz-Sypniewska
Jacek
J
Manitius
D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D018763:Muscle Fatigue; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000473:pathology; D009392:Nephrectomy / Q000379:methods*; D010369:Pectoralis Muscles / Q000098:blood supply* / Q000473:pathology; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012039:Regional Blood Flow; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index