Role of adenosine A(1) receptor in angiotensin II- and norepinephrine-induced renal vasoconstriction.
We investigated the contributions of adenosine A(1) 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 microg/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 microg/kg/min, n = 6). Blockade of adenosine A(1) receptors with 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902; 10 microg/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 microg/kg/min) nor KW-3902 (10 microg/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 A(1) 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.
Aki
Yasuharu
Y
Department of Pharmacology, Kagawa Medical University, Japan.
Nishiyama
Akira
A
Miyatake
Akira
A
Kimura
Shoji
S
Kohno
Masakazu
M
Abe
Youichi
Y
D000241:Adenosine / Q000494:pharmacology / Q000502:physiology; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004232:Diuretics; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007261:Infusions, Intra-Arterial; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology
D004232:Diuretics; D018047:Receptors, Purinergic P1; D014970:Xanthines; D000804:Angiotensin II; C073525:rolofylline; D000241:Adenosine; D009638:Norepinephrine