title: Renal interstitial adenosine is increased in angiotensin II-induced hypertensive rats.
abstract: Since marked renal vasoconstriction is observed in angiotensin II (ANG II)-mediated hypertensive rats, we studied the possible interaction between ANG II and adenosine in this model. ANG II was infused into male Wistar rats through osmotic minipumps (435 ng x kg(-1) x min(-1)) for 14 days. In sham and ANG II groups, renal tissue and interstitial adenosine were measured; both increased to a similar twofold extent in the ANG II-treated rats (31.40 +/- 4 vs. 62.0 +/- 8.4 nM, sham vs. ANG II, interstitial adenosine; P< 0.001). The latter decreased by 47% with the specific blockade of 5'-nucleotidase. Glomerular hemodynamics demonstrated marked renal vasoconstriction in the angiotensin-treated group, which was reverted by an adenosine A(1)-receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine, 10 mug.kg(-1) x min(-1)). 5'-Nucleotidase and adenosine deaminase (ADA) activities were measured in the cytosolic and membrane fractions. Only the membrane ADA activity decreased from 1,202 +/- 80 to 900 +/- 50 mU/mg protein in the ANG II-treated rats (P< 0.05), as well as in their protein and mRNA expression. Despite the adenosine elevation, A(1) and A(2b) receptor protein did not change; in contrast, downregulation was observed in A(2a) receptor and upregulation in A(3) receptor. A similar pattern was found in the cortex and in the medulla; mRNA significantly decreased only in the A(3) receptor in both segments. These results suggest that the elevation of renal tissue and interstitial adenosine contributes to the renal vasoconstriction observed in the ANG II-induced hypertension and that it is mediated by a decrease in the activity and expression of ADA, increased production of adenosine, and an induced imbalance in adenosine receptors.
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Mexico City, Mexico. marthafranco@lycos.com
authors.forename: Martha
authors.initials: M
authors.lastname: Franco
authors.forename: Rocio
authors.initials: R
authors.lastname: Bautista
authors.forename: Oscar
authors.initials: O
authors.lastname: Pérez-Méndez
authors.forename: Lidia
authors.initials: L
authors.lastname: González
authors.forename: Ursino
authors.initials: U
authors.lastname: Pacheco
authors.forename: L G
authors.initials: LG
authors.lastname: Sánchez-Lozada
authors.forename: José
authors.initials: J
authors.lastname: Santamaría
authors.forename: Edilia
authors.initials: E
authors.lastname: Tapia
authors.forename: Rogelio
authors.initials: R
authors.lastname: Monreal
authors.forename: Flavio
authors.initials: F
authors.lastname: Martínez
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000378:metabolism; D000804:Angiotensin II / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D011507:Proteinuria / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000009:adverse effects
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D015720:5'-Nucleotidase; D000243:Adenosine Deaminase; D000241:Adenosine