Role of Adenosine A1 Receptor in Angiotensin II- and Norepinephrine-Induced Renal Vasoconstriction

Publisher Website
Google Scholar
Abstract
We investigated the contributions of adenosine A1 receptors to angiotensin II- and norepinephrine-induced renal vasoconstriction. Intrarenal administrations of angiotensin II (3, 10, and 30 ng) or norepinephrine (100 and 500 ng) produced dose-dependent renal vasoconstriction in anesthetized dogs. Under resting conditions, angiotensin II (30 ng) and norepinephrine (500 ng) significantly decreased renal blood flow by −43 ± 3 and −19 ± 2%, respectively (n = 21). Intra-arterial infusion of adenosine (5 μg/kg/min) significantly augmented renal blood flow responses to both angiotensin II and norepinephrine (−64 ± 4 and −45 ± 14%, n = 7). Renal blood flow responses to angiotensin II and norepinephrine were also augmented by inhibition of cellular uptake of adenosine with dipyridamole (10 μg/kg/min, n = 6). Blockade of adenosine A1 receptors with 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902; 10 μg/kg/min) did not alter basal renal blood flow but significantly attenuated angiotensin II- and norepinephrine-induced renal vasoconstriction (−34 ± 6 and −9 ± 3%, n = 7). Furthermore, KW-3902 completely prevented augmentation of renal blood flow responses to angiotensin II and norepinephrine produced by adenosine or dipyridamole (n = 7 and 6, respectively). Administrations of angiotensin II (30 ng) or norepinephrine (500 ng) into the common carotid artery significantly decreased carotid blood flow by −20 ± 5 and −41 ± 10%, respectively; however, neither adenosine (5 μg/kg/min) nor KW-3902 (10 μg/kg/min) affected the carotid blood flow responses to angiotensin II and norepinephrine (n = 5, respectively). Adenosine concentrations in dialysates were not significantly changed by administrations of angiotensin II (from 19 ± 3 to 24 ± 4 nM, n = 6) or norepinephrine (from 16 ± 3 to 19 ± 3 nM,n = 6). These results suggest that basal interstitial adenosine levels influence both angiotensin II and norepinephrine-induced vasoconstriction via A1 receptors in the kidney but not in the area drained by the common carotid artery. The responses of adenosine to angiotensin II- and norepinephrine-induced renal vasoconstriction may not be mediated through de novo intrarenal adenosine accumulation due to angiotensin II- and norepinephrine-induced renal vasoconstriction.