Differential changes in vascular mRNA levels between rat iliac and renal arteries produced by cessation of voluntary running

Abstract

New Findings: • What is the central question of this study? While it is well accepted that long-term physical inactivity is associated with an increased cardiovascular risk, the early effects of adoption of a sedentary lifestyle on the vasculature have not been characterized at the molecular level. • What is the main finding and its importance? The primary finding of this study is that transition from high to low physical activity produces modest changes in mRNA expression for some pro-and anti-atherogenic genes, but that both the genes affected and direction of change differ between iliac and renal artery. This heterogeneous effect of short-term physical inactivity could be attributed to the distinct alterations in haemodynamic forces between these arteries. Early vascular changes at the molecular level caused by adoption of a sedentary lifestyle are incompletely characterized. Herein, we employed the rodent wheel-lock model to identify mRNAs in the arterial wall that are responsive to the acute transition from higher to lower levels of daily physical activity. Specifically, we evaluated whether short-term cessation of voluntary wheel running alters vascular mRNA levels in rat conduit arteries previously reported to have marked increases (i.e. iliac artery) versus marked decreases (i.e. renal artery) in blood flow during running. We used young female Wistar rats with free access to voluntary running wheels. Following 23 days of voluntary running (average distance of ∼15 km per night; ∼4.4 h per night), rats in one group were rapidly transitioned to a sedentary state by locking the wheels for 7 days (n= 9; wheel-lock 7 day rats) or remained active in a second group for an additional 7 days (n= 9; wheel-lock 0 day rats). Real-time PCR was conducted on total RNA isolated from iliac and renal arteries to evaluate expression of 25 pro-atherogenic and anti-atherogenic genes. Compared with the iliac arteries of wheel-lock 0 day rats, iliac arteries of wheel-lock 7 day rats exhibited increased expression of TNFR1 (+19%), ET1 (+59%) and LOX-1 (+31%; all P < 0.05). Moreover, compared with renal arteries of wheel-lock 0 day rats, renal arteries of wheel-lock 7 day rats exhibited decreased expression of ETb (-23%), p47phox (-32%) and p67phox (-19%; all P < 0.05). These data demonstrate that cessation of voluntary wheel running for 7 days produces modest, but differential changes in mRNA levels between the iliac and renal arteries of healthy rats. This heterogeneous influence of short-term physical inactivity could be attributed to the distinct alteration in haemodynamic forces between arteries. © 2012 The Authors. Experimental Physiology © 2012 The Physiological Society.