Vol. 303, Issue 1, 117-123, October 2002

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

Yasuharu Aki¹ , Akira Nishiyama, Akira Miyatake, Shoji Kimura, Masakazu Kohno and Youichi Abe

Department of Pharmacology (Ya.A., A.N., S.K., Yo.A.), Research Equipment Center (A.M.), and Second Department of Internal Medicine (M.K.), Kagawa Medical University, Kagawa, Japan.

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.