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Abstract
L-NAME-induced hypertension is commonly used to study endothelial dysfunction and
related vascular effects. It has been reported that genetic deletion of A 1 adenosine
receptor (AR) reduces blood pressure (BP) increases in mice and thus, suggesting the
involvement of A 1 AR. Thus, we sought to determine whether A 1 AR-induced vascular
responses were altered in this mouse model of hypertension. L-NAME (1 mg/ml) was given
in the drinking water for 28 days to mice. The BP was monitored using non-invasive
tail-cuff system. Muscle tension studies were performed using DMT for mesenteric arteries
(MAs) and organ bath for aorta. Protein expression was analyzed by western blot. Significantly,
higher systolic and mean arterial blood pressure was noted in L-NAME mice. In MAs,
higher 2-Chloro-N 6 -cyclopentyladenosine (CCPA, selective A 1 AR agonist) induced
contractions in hypertensive mice were observed. This enhanced contraction was inhibited
by HET0016 (Cytochrome 450 4A inhibitor, 10 µM, 15 min). Contrary, 5′-(N-Ethylcarboxamido)
adenosine (NECA, non-selective AR agonist) induced vascular responses were comparable
in both groups. Pinacidil (K ATP channel opener) induced relaxation was significantly
increased in hypertensive mice. In aorta, CCPA-induced contractions were enhanced
and inhibited by HET0016 in hypertensive mice. Notably, NECA-induced contractions
in aorta were enhanced in hypertensive mice. Higher expressions of A 1 AR and Cyp4A
were noted in MAs of hypertensive mice. In addition, in aorta, higher A 1 AR and comparable
Cyp4A levels were observed in hypertensive mice. A 1 AR-induced vascular contractions
were enhanced in hypertensive mice aorta and MAs. Cyp4A plays a role in altered vascular
responses in MAs.