Effects of Aging on Integrin‐Mediated Vascular Smooth Muscle Contractility in Soleus Muscle Feed Arteries

Abstract

Introduction Vasoconstrictor responses decline with age in soleus muscle feed arteries (SFA). Previous data from our laboratory revealed that alterations in integrin signaling contributed to the impaired constrictor responses. Whether the impaired constrictor responses resulted from integrin signaling in endothelial cells or vascular smooth muscle (VSM) cells is unknown. Thus, the purpose of the study was to test the hypothesis that aging alters VSM contractility due to impaired VSM integrin signaling in SFA. Method Soleus muscle feed arteries (SFA) were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats. SFA were cannulated with glass micropipettes and pressurized to 90 cm H2O for assessment of vasoconstrictor function. To isolate the role of smooth muscle in constrictor responses, endothelial cells were removed (denuded) by passing 5 ml of air through the lumen of the artery. Vasoconstrictor responses were assessed using increasing whole log doses of norepinephrine (NE; 10-9-10-4 M), angiotensin II (Ang II; 10-11-10-7 M), and phenylephrine (PE; 10-9-10-4 M) in the presence or absence of RGD, an integrin inhibitory peptide, and RGE, as control. Results Vasoconstrictor responses to NE, PE, and Ang II were less in old denuded SFA when compared to young SFA. In the presence of RGD, the constrictor response to Ang II (not NE or PE) was significantly reduced in both young and old SFA. RGE did not alter the constrictor responses to any of the agonists. Conclusion The results of this study indicate that VSM contractility declines with age in SFA. In addition, our results suggest that RGD binding integrin-mediated constrictor function declines with age in denuded SFA.