Remodeling of the skeletal muscle microcirculation increases resistance to perfusion in obese Zucker rats

Abstract

Whereas previous studies have demonstrated that the development of syndrome X in obese Zucker rats (OZR) is associated with impaired arteriolar reactivity to vasoactive stimuli, additional results from these studies indicate that the passive diameter of skeletal muscle arterioles is reduced in OZR versus lean Zucker rats (LZR). On the basis of these prior observations, the present study evaluated structural alterations to the skeletal muscle microcirculation as potential contributors to an elevated vascular resistance. Isolated skeletal muscle resistance arterioles exhibited a reduced passive diameter at all levels of intralumenal pressure and a left-shifted stress-strain curve in OZR versus LZR, indicative of structural remodeling of individual arterioles. Histological analyses using Griffonia simplicifolia I lectin-stained sections of skeletal muscle demonstrated reduced microvessel density (rarefaction) in OZR versus LZR, suggesting remodeling of entire microvascular networks. Finally, under maximally dilated conditions, constant flow-perfused skeletal muscle of OZR exhibited significant elevations in perfusion pressure versus LZR, indicative of an increased resistance to perfusion within the microcirculation. These data suggest that developing structural alterations to the skeletal muscle microcirculation in OZR result in elevated vascular resistance, which may, acting in concert with impaired arteriolar reactivity, contribute to blunted active hyperemic responses and compromised performance of in situ skeletal muscle with elevated metabolic demand.

Differential structural and functional changes in penile and coronary arteries from obese Zucker rats

“…Vascular remodeling has recently been reported in asymptomatic middle-aged women with metabolic syndrome, where carotid artery measurements by noninvasive B-mode ultrasound technique showed a preserved luminal diameter and blood flow in response to arterial wall thickening (24). On the other hand, skeletal muscle resistance arterioles of OZRs have consistently been demonstrated to remodel, resulting in a reduced passive diameter and distensibility but also thinner walls, indicative of atrophic vascular remodeling (11,45). Our results in the small PAs of OZRs would be in agreement with those reported in subcutaneous resistance arteries from type 2 diabetic patients, which displayed inward hypertrophic remod- eling with reduced lumen diameters and an increased mediato-lumen ratio (43).…”

“…However, under these metabolic conditions, structure in CAs was preserved, suggesting that factors other than the metabolic ones may additionally be involved in the genesis of the vascular remodeling observed in PAs. Studies in OZRs have suggested that remodeling of the microcirculation reflects chronic reductions in blood flow secondary to abnormal vascular reactivity (11,45). Decreased NO bioavailability and reduced endothelium-dependent relaxations have recently been associated with the vascular remodeling in resistance arteries from OZRs (4).…”

Integration of skeletal muscle resistance arteriolar reactivity for perfusion responses in the metabolic syndrome

“…Subsequently, arterioles were treated with the superoxide dismutase mimetic Tempol (10 Ϫ4 M) or the antagonist for the prostaglandin H2/thromboxane A2 (PGH2/TxA2) receptor SQ-29548 (10 Ϫ5 M) to assess the contribution of vascular oxidant stress and alterations to arachidonic acid metabolism. At the conclusion of all experiments involving isolated arterioles, arteriolar wall mechanics were assessed under Ca 2ϩ -free conditions as described previously (2,12). Preparation of in situ blood-perfused hindlimb.…”

“…Preparation of in situ blood-perfused hindlimb. The left hindlimb of each animal was isolated in situ (11,12), and the sciatic nerve was tied into a stimulating electrode. A microcirculation flow probe (Transonic 0.5/0.7 PS) was placed on the femoral artery to monitor muscle perfusion, and heparin (1500 IU/kg) was infused via the jugular vein to prevent blood coagulation.…”

Preserved coronary arteriolar dilatation in patients with type 2 diabetes mellitus: Implications for reactive oxygen species

“…Before the morphological changes take place [18,19,26,45,57], vasomotor dysfunction of microvessels may occur, which is considered to be one of the early alterations that occur in several cardiovascular diseases, as outlined by many recent reviews [9,11,12,29,32,44]. In humans with diabetes mellitus, impaired vasomotor function of the large conductance arteries is established [14].…”