Initiation of reticular and spider veins, incompetent perforantes and varicose veins in the saphenous vein network of the rat.

In an attempt to induce experimental varicosity, reverse perforant vein development was initiated in the rat leg by applying a chronic (14 and 32 weeks) partial stricture on the main branch of the deep femoral vein. At surfacing of the incompetent perforantes, typical reticular vein plaques and spider veins were identified by video-microscopy and quantitative histology. Deep vein blood was channeled by them into the saphenous vein system, the extra flow deforming these vessels, causing local dilations and broken course, even undulations of larger branches.

Morphological remodeling of the intramural coronary resistance artery network geometry in chronically Angiotensin II infused hypertensive female rats.

Segmental remodeling of resistance arteries, inhibition of angiogenetic processes, their rarefaction by AngiotensinII and hypertension are accepted facts. Less is known about alterations in resistance artery network geometry potentially induced by them. Female rats were infused with 100 ng/kg/min AngiotensinII with osmotic minipumps for four weeks that raised mean arterial blood pressure from 98 ± 3 to 125 ± 7 mmHg. Geometry of the left coronary artery system was studied on plastic casts and on in situ microsurgically prepared, saline infused video-microscoped networks (n = 13 and 11 controls and hypertensives, respectively). Parallel running branches, broken course of larger branches, multiple branchings and branch crossings have been identified (13 and 74 such deformities, in control and hypertensive networks, respectively, p < 0.01). Bifurcation angles increased with increasing asymmetry of daughter branches but not in hypertensives. Dividing the whole network (theoretically) into several hundreds of 50µm long ring units, ring frequency peaked at 200µm diameter in normal networks. This peak diminished and was replaced by a peak at 300µm in hypertensives (p < 0.01). In controls, diameter of vascular units decreased at a fairly even rate with flow distance from the orifice. The 350, 200, 150µm diameter units were found with highest frequencies at flow distances around 2.5, 5.5 and 7.5mm, respectively. This regular pattern disintegrated in hypertensives. Higher blood flow routes were needed to cover the same distance from the orifice (p < 0.01). Shrinkage and diminishment of many parallel connected 200µm segments, concomitant enlargement of many larger segments accompanied with morphological deformities can be expected to contribute to elevated vascular resistance.

Vascular KATP channels mitigate severe muscle O2 delivery-utilization mismatch during contractions in chronic heart failure rats.

The vascular ATP-sensitive K+ (KATP) channel is a mediator of skeletal muscle microvascular oxygenation (PO2mv) during contractions in health. We tested the hypothesis that KATP channel function is preserved in chronic heart failure (CHF) and therefore its inhibition would reduce PO2mv and exacerbate the time taken to reach the PO2mv steady-state during contractions of the spinotrapezius muscle. Moreover, we hypothesized that subsequent KATP channel activation would oppose the effects of this inhibition. Muscle PO2mv (phosphorescence quenching) was measured during 180s of 1-Hz twitch contractions (∼6V) under control, glibenclamide (GLI, KATP channel antagonist; 5mg/kg) and pinacidil (PIN, KATP channel agonist; 5mg/kg) conditions in 16 male Sprague-Dawley rats with CHF induced via myocardial infarction (coronary artery ligation, left ventricular end-diastolic pressure: 18±1mmHg). GLI reduced baseline PO2mv (control: 28.3±0.9, GLI: 24.8±1.0mmHg, p<0.05), lowered mean PO2mv (average PO2mv during the overall time taken to reach the steady-state; control: 20.6±0.6, GLI: 17.6±0.3mmHg, p<0.05), and slowed the attainment of steady-state PO2mv (overall mean response time; control: 66.1±10.2, GLI: 93.6±7.8s, p<0.05). PIN opposed these effects on the baseline PO2mv, mean PO2mv and time to reach the steady-state PO2mv (p<0.05 for all vs. GLI). Inhibition of KATP channels exacerbates the transient mismatch between muscle O2 delivery and utilization in CHF rats and this effect is opposed by PIN. These data reveal that the KATP channel constitutes one of the select few well-preserved mechanisms of skeletal muscle microvascular oxygenation control in CHF.