Altered post‐capillary and collecting venular reactivity in skeletal muscle with metabolic syndrome

Abstract

While research into vascular outcomes of the metabolic syndrome has focused on arterial/arteriolar and capillary levels, investigation into venular function and how this impacts responses has received little attention. Using the in situ cremaster muscle of obese Zucker rats (OZR; with lean Zucker rats (LZR) as controls), we determined indices of venular function. At ∼17 weeks of age, skeletal muscle post-capillary venular density was reduced by ∼20% in LZR vs. OZR, although there was no evidence of remodelling of the venular wall. Venular tone at ∼25 μm (post-capillary) and ∼75 μm (collecting) diameter was elevated in OZR vs. LZR. Venular dilatation to acetylcholine was blunted in OZR vs. LZR due to increased oxidant stress-based loss of nitric oxide bioavailability (post-capillary) and increased α - (and α -) mediated constrictor tone (collecting). Venular constrictor responses in OZR were comparable to LZR for most stimuli, although constriction to α -adrenoreceptor stimulation was elevated. In response to field stimulation of the cremaster muscle (0.5, 1, 3 Hz), venular dilator and hyperaemic responses to lower frequencies were blunted in OZR, but responses at 3 Hz were similar between strains. Venous production of TxA was higher in OZR than LZR and significantly higher than PGI production in either following arachidonic acid challenge. These results suggest that multi-faceted alterations to skeletal muscle venular function in OZR may contribute to alterations in upstream capillary pressure profiles and the transcapillary exchange of solutes and water under conditions of metabolic syndrome.

Role of capillary pericytes in the integration of spontaneous Ca2+ transients in the suburothelial microvasculature in situ of the mouse bladder

“…In skeletal muscle, increased tone in PCVs and venules in rat models with metabolic syndrome was reported and it was suggested to contribute to the altered capillary exchange (Lemaster et al . ).…”

“…Spontaneous constrictions in venules may facilitate venular drainage (Dongaonkar et al 2012). In skeletal muscle, increased tone in PCVs and venules in rat models with metabolic syndrome was reported and it was suggested to contribute to the altered capillary exchange (Lemaster et al 2017).…”

Skeletal muscle performance in metabolic disease: Microvascular or mitochondrial limitation or both?

“…While there have been reports of alterations to venular and lymphatic function with the development of chronic metabolic disease, the impact of these effects on tissue/organ function with alterations to metabolic demand and the regulation of blood flow are unclear at present. Additional investigation will be required to determine if alterations in venular function are sufficiently significant to impact hemodynamics in the upstream capillaries and compromise mass transport and exchange to a meaningful extent.…”

Tracking Cell Recruitment and Behavior within the Tumor Microenvironment Using Advanced Intravital Imaging Approaches

“…The application of either multiphoton ( Figure 3 a,b) or confocal IVM ( Figure 3 c–e) to the TME enabled the identification and characterization of the tumor vasculature. Using multiphoton imaging, arteries and arterioles were clearly discernable because of the presence of collagen in the vessel wall ( Figure 3 a,b), a protein that naturally fluoresces as a result of second-harmonic generation (colored in cyan) [ 35 , 36 , 37 , 38 ]. In comparison, the collecting venules, ranging in diameter from 50 µm to >250 µm, appeared as thin-walled structures without collagen, had few branch points, and ran parallel to the arterioles.…”