Table 1. Studies of the microcirculation in animal models of CKD: skeletal muscle.
| Author | Year | Species (strain); organ examined | CKD model; CKD duration |
Main findings | Rarefaction [%] Compared with controls (method) |
Ref. |
|---|---|---|---|---|---|---|
| Lombard et al. | 1989 | Rat (Sprague–Dawley); M. cremaster |
¾ NX; short-term HTN (NaCl infusion, 36 h); long-term HTN (4% NaCl in diet 5–6 weeks) | Arterioles were constricted (35–50%) in rats with short term (36 h), but not chronic (5–6 weeks) CKD + hypertension (HTN) | 15% in long-term HTN (Microfil sections) |
[13] |
| Hansen-Smith et al. | 1990 | Rat (Sprague–Dawley); M. cremaster |
¾ NX, HTN (4% NaCl in diet); 4 weeks | Degenerative changes in small- and medium-sized arterioles with loss of endothelial and smooth muscle cells | Proof of anatomic rarefaction (light and electron microscopy) |
[10] |
| Hernandez and Greene | 1995 | Rat (Sprague–Dawley); M. biceps femoralis |
¾ NX; after 10 days, switch from a low-salt to a high-salt diet | Progressive HTN and vascular resistance, decreasing tissue blood flow and MV density during observation (5–28 days) | 25%; (day 10) (videomicroscopy fluorescence) |
[16] |
| Hansen-Smith et al. | 1996 | Rat (Sprague–Dawley); M. cremaster |
¾ NX; short-term HTN (3 days, 4% NaCl in diet) | MV rarefaction in both CKD and sham-op. controls after salt loading | 22–24%, staining of third and fourth orders’ arterioles (lectin staining) | [14] |
| Amann et al. | 1997 | Rat (Sprague–Dawley) M. psoas and heart |
5/6 NX; CKD for 8 weeks | HTN; myocyte cross-sectional area and interstitial tissue increased, MV density reduced in the heart but unchanged in M. psoas | 23% in heart, none in M. psoas (stereological evaluation) |
[24] |
| Jacobi et al. | 2006 | Rat (Sprague–Dawley) M. gastrocnemius (locomotor) M. soleus (locomotor) |
5/6 NX + hindlimb ischemia CKD for 12 weeks |
No HTN; MV unchanged compared with controls at baseline in MG and MS, but increase after ischemia diminished in 5/6 NX rats | No rarefaction, but less increase in MV density after ischemia in CKD animals (CD31 IF) |
[22] |
| Flisinski et al. | 2008 | Rat (Wistar) M. gastrocnemius (MG; locomotor), M. longissimus thoracis (ML; statomotor) |
½ NX or 5/6 NX; CKD for 4 weeks |
½ NX normotensive; 5/6 NX had HTN Significant rarefaction in both stages independent of HTN, similar decrease in capillary/fiber ratio; changes differ in muscles (MG >> ML) |
MG: 56% (½ NX), 48% (5/6 NX) ML: 33% (½ NX), 11% (5/6 NX) (Staining, alkaline phosphatase) |
[17] |
| Flisinski et al. | 2012 | Rat (Wistar) M. gastrocnemius (MG; locomotor), M. longissimus thoracis (ML; statomotor) |
½ NX or 5/6 NX; CKD for 6 weeks |
Decreased expression of HIF-1α, VEGF, VEGF-R1,2 only in MG. Increased HIF-1α protein, iNOS in ML | Not examined | [21] |
| Schellinger et al. | 2017 | Rat (Sprague–Dawley) M. gastrocnemius |
5/6 NX CKD for 8 weeks + hindlimb ischemia for 2 weeks + HIF-1α stabilization by carbon monoxide or prolyl-hydroxylase inhibitor |
MV density decreased after ischemia, but not at baseline compared with sham-op. Post-ischemic MV sprouting impaired in CKD, restored by HIF-1α stabilization |
No rarefaction, but no increase in MV density after ischemia in CKD animals | [23] |
| Prommer and Maurer et al. | 2018 | Mouse (BALB/c) M. cremaster Heart |
5/6 NX; adenine feeding (0.2%) CKD for 4 months (5/6 NX) or for 4 weeks (adenine) |
No HTN; loss of coherent MV networks, large avascular areas, diminished bloodflow velocity, vascular tone, oxygen uptake, MV rarefaction in the cremaster muscle paralleled rarefaction in the myocardium. Decrease in mRNA levels of HIF-1α, Angpt-2, TIE-1 and TIE-2, Flkt-1 and MMP-9 in the heart |
Progressive rarefaction with increasing severity of CKD (serum urea levels). Mean: 34% (5/6 NX); 43% (adenine) | [18] |
Abbreviations: ACEi, angiotensin-converting enzyme inhibitor; HIF, hypoxia-inducible factor; HTN, hypertension; IF, immunofluorescence; iNOS, inducible NO synthase; MV, microvascular; NX, nephrectomy; sham-op., sham operated.