Reduction In Capillary Flow Research Articles

Renal Microvascular Disease Predicts Renal Function in Diabetes

Renal microvascular disease reflected directly by peritubular capillary flow reduction and indirectly by renal function impairment has been documented in early diabetic nephropathy (DN) associated with normoalbuminuria and normal serum creatinine concentration. The renal microvascular disease observed in early DN [chronic kidney disease (CKD) stages 1–2] could progress under current practice to late DN (CKD stages 3–5) with a further reduction in peritubular capillary flow. This advanced renal microvascular disease in late DN is characterized by therapeutic resistance to vasodilators and altered vascular homeostasis associated with impaired nitric oxide production. The renal microvascular disease is progressive as the disease severity progresses and eventually induces chronic renal ischemia and a progressive tubulointerstitial fibrosis. Further study has revealed that early DN is associated with an adequately functional vascular homeostasis. Therefore, recognition and treatment of early renal microvascular disease at early DN (stages 1–2) could enhance renal perfusion and restore renal function.

Therapeutic strategy towards renal restoration in chronic kidney disease

Background: The population with end-stage renal disease is increasing. This continued growth is related to: i) diagnostic failure in screening for early chronic kidney disease (CKD) associated with tubulointerstitial fibrosis (TIF), ii) failure in preventing renal disease progression due to lack of understanding of the precise determinants that induce TIF, and iii) delayed treatment which simply slows renal disease progression, but is unable to restore renal function. Objective: To review therapeutic strategy to restore renal function in CKD stressing fractional excretion of magnesium (FE Mg) as a sensitive biomarker for screening early CKD associated with TIF. Results: There is much evidence to support the crucial role of renal microvascular disease as the determinant of TIF and disease progression. A unique pattern of hemodynamic maladjustment is characterized by a preferential constriction of the efferent arteriole that induces peritubular capillary flow reduction in CKDs. Conclusion: The present information leads to a therapeutic strategy to restore renal function in early CKD patients.

肺高血圧ラット右室冠毛細管における内皮グリコカリックスの減少を伴う内壁リモデリングとヘモダイナミクスの変化

We hypothesized that coronary capillary function is impaired with a decreased glycocalyx layer and uneven inner wall remodeling in right ventricles that are hypertrophied due to pulmonary hypertension (PH). Five-week-old male Sprague-Dawley rats were divided into 2 groups (PH: n=25, control: n=27). In the PH group, Monocrotaline (60 mg/kg SC) was administrated at 5 weeks. Coronary capillary hemodynamics was visualized in vivo at 8 weeks of age using our high-resolution intravital videomicrosopy, and RBC velocities in RV capillaries were evaluated, along with capillary diameters. Configuration of the capillary cast was assessed by a confocal laser scanning microscope. The thickness of the glycocalyx on the capillary endothelial surface was evaluated with Alcian blue 8GX by electron microscopy. RV systolic pressure increased in PH (by 142%, p<0.01). The diameters of capillaries were uneven in PH (coefficient of variation of diameters along capillary trees; 24±8% vs. 11±3%, p<0.05). The thickness of the glycocalyx in PH was less than half that of control (0.20±0.05 vs. 0.45±0.14 μm, p<0.05). RBC velocity was decreased in PH (820±110 vs. 1,100±230 μm/sec, p<0.05). The capillary flow reduction in PH may be closely related to the changes in the glycocalyx and vessel irregularity, resulting in insufficient oxygen supply to the heart.

Renal Microvascular Disease in an Aging Population: A Reversible Process?

Renal microvascular disease and tubulointerstitial fibrosis are usually demonstrated in aging in humans and animals. It has recently been proposed that renal microvascular disease is the crucial determinant of tubulointerstitial disease or fibrosis. Enhanced circulating endothelial cell loss is a biomarker that reflects glomerular endothelial injury or renal microvascular disease, and fractional excretion of magnesium (FE Mg) is a sensitive biomarker that reflects an early stage of tubulointerstitial fibrosis. In aging in humans, both of these biomarkers are abnormally elevated. In addition, a glomerular endothelial dysfunction determined by altered hemodynamics associated with peritubular capillary flow reduction is substantiated. A correction of such hemodynamic alteration with vasodilators can effectively improve renal perfusion and restore renal function. Thus, anti-aging therapy can reverse the renal microvascular disease and dysfunction associated with the aging process.

Adrenergic and dopaminergic control of the canine paw microcirculation

Basal isolated canine paw blood flow was equally distributed between arteriovenous anastomosis (AVA) and capillary circulations. Norepinephrine decreased AVA flow by 92% and capillary flow by 41%. Dopamine significantly reduced AVA flow by 94% compared to baseline with a 37% reduction in capillary flow. However, with α-adrenergic blockade dopamine decreased AVA flow 66% while capillary flow increased 42%. Isoproterenol increased capillary flow almost twofold and appeared to decrease AVA flow, although the latter was statistically insignificant. Differential effects of adrenergic and dopaminergic agonists on canine paw AVA and capillary blood flow suggest the existence of independent regulation of these components of the microcirculation.

Cessation of capillary blood flow induced by localized application of carbon dioxide.

A small test area of the pulmonary capillary bed of frog's lung was exposed to carbon dioxide. The capillary bed was observed by means of a dark field episcopal microscope and recorded on video tapes via a TV-camera. Swollen capillaries forming a hexagonal network surrounded concave alveolar cells. The flow velocity of red blood cells through capillaries was reduced to 17.5% of the flow velocity during the control condition by the application of the moistened gas mixture containing 30% CO2. The blood flow in capillaries ceased when wet 100% CO2 was applied to the test area. Red blood cells were packed in capillaries. They disaggregated by the introduction of air in five seconds and were quickly flowing in an elongated leaflet shape in 30 seconds after the introduction of air.

Norepinephrine and phenoxybenzamine redistribution of dog forelimb blood flow and volume.

SummaryDog forelimbs were perfused under constant blood flow conditions. Norepinephrine significantly increased blood flow resistance and decreased total and active vascular volumes. 86Rb recovery was increased. Phenoxybenzamine returned the resistance to control without changing total vascular volume or red cells-51Cr volume. However, albumin-13I space was increased with no change in 86Rb recovery. Norepinephrine caused a reduction in capillary flow with redistribution of flow to shunt vessels. Alpha blockade allowed opening of circulatory areas constructed at least in part of nonexchange vessels.

The effect of nicotine on regional blood flow in the the canine heart.

SummaryThe effect of nicotine administration on regional myocardial blood flow was examined in normal hearts and after partial coronary artery occlusion. Under normal circumstances as well as after infusion of nicotine in normal hearts the subendocardial portion of the myocardium had a higher capillary flow than the subepicardial fraction. Partial coronary artery constriction alone did not alter this relationship; however, when it was followed by infusion of nicotine, a significant reduction in capillary flow in the inner portion of the myocardium compared to the outer part was observed.