title: Caffeine potentiates the renin response to furosemide in rats. Evidence for a regulatory role of endogenous adenosine.
abstract: Adenosine is a potent inhibitor of renin release. It has therefore been suggested that endogenous adenosine may play a role in the regulation of renin release. Sodium-chloride transport at the level of the macula densa has been proposed as the primary source of endogenous adenosine. Evidence to support a modulatory role of adenosine on renin release in vivo is, however, limited. We therefore wanted to determine if: 1) adenosine modulates furosemide-induced renin release and 2) sodium-chloride reabsorption at the macula densa is essential for adenosine actions. To test these hypotheses, three groups of rats were pretreated either with saline or the adenosine receptor antagonists caffeine or 1,3-dipropyl-8-(p-sulfophenyl)xanthine (both at a dose of 30 mg/kg followed by 450 micrograms/kg/min). Rats then received furosemide (50 mg/kg i.v.). In the vehicle group, furosemide increased urinary volume, sodium and potassium excretion and increased plasma renin activity from 6 +/- 1 to 45 +/- 11 ngAl/ml/hr. Caffeine and 1,3-dipropyl-8-(p-sulfophenyl)xanthine potentiated the increase in plasma renin activity produced by furosemide (to 120 +/- 15 and 147 +/- 21 ng Al/ml/hr, respectively), whereas having no significant effects on urinary volume, sodium excretion or blood pressure. These results suggest that furosemide-induced renin release in vivo is restrained by endogenous adenosine. In as much as furosemide blocks sodium-chloride transport in the thick ascending limb of Henle's loop and the macula densa cells, it appears that under the conditions of this study sodium transport across these segments is not essential to initiate adenosine-mediated mechanisms.
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee.
authors.forename: S
authors.initials: S
authors.lastname: Paul
authors.forename: E K
authors.initials: EK
authors.lastname: Jackson
authors.forename: D
authors.initials: D
authors.lastname: Robertson
authors.forename: R A
authors.initials: RA
authors.lastname: Branch
authors.forename: I
authors.initials: I
authors.lastname: Biaggioni
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D004357:Drug Synergism; D005665:Furosemide / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D014970:Xanthines; D002110:Caffeine; D005665:Furosemide; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D012083:Renin; D000241:Adenosine