title: Adenosine causes the release of active renin and angiotensin II in the coronary circulation of patients with essential hypertension.
abstract: OBJECTIVE
  The aim of the study was to evaluate whether adenosine infusion can induce production of active renin and angiotensin II in human coronary circulation.
  
  
  BACKGROUND
  Adenosine can activate angiotensin production in the forearm vessels of essential hypertensive patients.
  
  
  METHODS
  In six normotensive subjects and 12 essential hypertensive patients adenosine was infused into the left anterior descending coronary artery (1, 10, 100 and 1,000 microg/min x 5 min each) while active renin (radioimmunometric assay) and angiotensin II (radioimmunoassay after high performance liquid chromatography purification) were measured in venous (great cardiac vein) and coronary arterial blood samples. In five out of 12 hypertensive patients adenosine infusion and plasma samples were repeated during intracoronary angiotensin-converting enzyme inhibitor benazeprilat (25 microg/min) administration. Finally, in adjunctive hypertensive patients, the same procedure was applied during intracoronary sodium nitroprusside (n = 4) or acetylcholine (n = 4).
  
  
  RESULTS
  In hypertensive patients, but not in control subjects, despite a similar increment in coronary blood flow, a significant (p < 0.05) transient increase of venous active renin (from 10.7 +/- 1.4 [95% confidence interval 9.4 to 11.8] to a maximum of 13.8 +/- 2.1 [12.2 to 15.5] with a consequent drop to 10.9 +/- 1.8 [9.7 to 12.1] pg/ml), and angiotensin II (from 14.6 +/- 2.0 [12.7 to 16.5] to a maximum of 20.4 +/- 2.7 [18.7 to 22.2] with a consequent drop to 16.3 +/- 1.8 [13.9 to 18.7] pg/ml) was observed under adenosine infusion, whereas arterial values did not change. Calculated venous-arterial active renin and angiotensin II release showed a strong correlation (r = 0.78 and r = 0.71, respectively; p < 0.001) with circulating active renin. This adenosine-induced venous angiotensin II increase was significantly blunted by benazeprilat. Finally, both sodium nitroprusside and acetylcholine did not affect arterial and venous values of active renin and angiotensin II.
  
  
  CONCLUSIONS
  These data indicate that exogenous adenosine stimulates the release of active renin and angiotensin II in the coronary arteries of essential hypertensive patients, and suggest that this phenomenon is probably due to renin release from tissue stores of renally derived renin.
authors.affiliation: Department of Internal Medicine, University of Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Virdis
authors.forename: L
authors.initials: L
authors.lastname: Ghiadoni
authors.forename: M
authors.initials: M
authors.lastname: Marzilli
authors.forename: E
authors.initials: E
authors.lastname: Orsini
authors.forename: S
authors.initials: S
authors.lastname: Favilla
authors.forename: P
authors.initials: P
authors.lastname: Duranti
authors.forename: S
authors.initials: S
authors.lastname: Taddei
authors.forename: P
authors.initials: P
authors.lastname: Marraccini
authors.forename: A
authors.initials: A
authors.lastname: Salvetti
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000328:Adult; D000804:Angiotensin II / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D006328:Cardiac Catheterization; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005542:Forearm / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D012083:Renin / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D000804:Angiotensin II; D009599:Nitroprusside; D012083:Renin; C052133:benazeprilat; D000241:Adenosine; D000109:Acetylcholine