Faculty Collaboration Database

Increased peripheral vascular disease risk progressively constrains perfusion adaptability in the skeletal muscle microcirculation. Am J Physiol Heart Circ Physiol 2016 Feb 15;310(4):H488-504

Date

12/25/2015

Pubmed ID

26702145

Pubmed Central ID

PMC4796615

DOI

10.1152/ajpheart.00790.2015

Scopus ID

2-s2.0-84958568627 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

To determine the impact of progressive elevations in peripheral vascular disease (PVD) risk on microvascular function, we utilized eight rat models spanning "healthy" to "high PVD risk" and used a multiscale approach to interrogate microvascular function and outcomes: healthy: Sprague-Dawley rats (SDR) and lean Zucker rats (LZR); mild risk: SDR on high-salt diet (HSD) and SDR on high-fructose diet (HFD); moderate risk: reduced renal mass-hypertensive rats (RRM) and spontaneously hypertensive rats (SHR); high risk: obese Zucker rats (OZR) and Dahl salt-sensitive rats (DSS). Vascular reactivity and biochemical analyses demonstrated that even mild elevations in PVD risk severely attenuated nitric oxide (NO) bioavailability and caused progressive shifts in arachidonic acid metabolism, increasing thromboxane A2 levels. With the introduction of hypertension, arteriolar myogenic activation and adrenergic constriction were increased. However, while functional hyperemia and fatigue resistance of in situ skeletal muscle were not impacted with mild or moderate PVD risk, blood oxygen handling suggested an increasingly heterogeneous perfusion within resting and contracting skeletal muscle. Analysis of in situ networks demonstrated an increasingly stable and heterogeneous distribution of perfusion at arteriolar bifurcations with elevated PVD risk, a phenomenon that was manifested first in the distal microcirculation and evolved proximally with increasing risk. The increased perfusion distribution heterogeneity and loss of flexibility throughout the microvascular network, the result of the combined effects on NO bioavailability, arachidonic acid metabolism, myogenic activation, and adrenergic constriction, may represent the most accurate predictor of the skeletal muscle microvasculopathy and poor health outcomes associated with chronic elevations in PVD risk.

Author List

Frisbee JC, Butcher JT, Frisbee SJ, Olfert IM, Chantler PD, Tabone LE, d'Audiffret AC, Shrader CD, Goodwill AG, Stapleton PA, Brooks SD, Brock RW, Lombard JH

MESH terms used to index this publication - Major topics in bold

Animals
Arterioles
Fructose
Hypertension, Renal
Microcirculation
Muscle, Skeletal
Nitric Oxide
Oxygen Consumption
Perfusion
Peripheral Vascular Diseases
Rats
Rats, Inbred Dahl
Rats, Inbred SHR
Rats, Sprague-Dawley
Rats, Zucker
Risk Assessment
Sodium, Dietary
Thromboxane A2