Interaction between angiotensin II (ANGII) receptor 1A (AT1AR) and adenosine receptors in the control of vascular function in mouse aorta and mesenteric arteries

Abstract

ANG II, a systemic vasoconstrictor and adenosine through its receptors (ARs) regulate vascular function. Recently, we have shown that acute ANG II stimulation enhanced A1AR dependent CYP4A mediated contraction in mesenteric arteries (MA). In addition, A2BAR dependent and partly KATP channel mediated relaxation was also reduced in MAs after ANG II stimulation (Yadav et al., 2015). Thus, suggesting a possible interaction between ARs and AT1R in the control of vascular function. The present study is designed to explore interaction between AR and AT1R. There are two types of AT1 receptors; AT1A is ubiquitously expressed where as AT1B expressed in aorta, resistance arteries, adrenal glands, pituitary, and hypothalamus. Considering ubiquitous tissue expression of AT1A receptors, we performed muscle tension studies in isolated MA and aorta from WT and AT1A KO mice. We used DMT wire myograph for MAs and organ bath for aortas to perform concentration response curves (CRCs) to various agonists. Our data showed a significant increase in contraction to A1AR agonist CCPA in MAs isolated from AT1A KO. The contraction observed at 10 and 100 nM of CCPA was 24.8 ± 13.7 (% PE) and 29.7 ± 14.8 in AT1A KO mice which was significantly higher compared to −4.8 ± 3.7 and 0.5 ± 3.2 observed in WT mice. NECA (non‐selective AR agonist) induced CRC was similar in WT and AT1A KO MAs. Pinacidil (KATP channel opener) and C21 (AT2 agonist) produced comparable CRCs in WT and AT1A KO MAs. In addition, comparable ACh, PE and KCl‐induced responses were present in MAs. In aorta, CRCs to CCPA, NECA, C21 and Pinacidil were comparable between WT and AT1A KO. However, PE‐induced contraction was significantly reduced in aorta of AT1A KO mice. ACh induced relaxation in aorta was 54.1 ± 4.4 (% PE) in AT1A KO compared to WT, 40.7±4.6 (p<0.05). Comparable contraction to ANG II in MAs suggests the involvement of AT1B receptors which needs further investigation. In conclusion, our data suggest an interaction between ARs and AT1A receptor in the control of vascular function.Support or Funding InformationSupported by HL 027339