Adenosine activates a vascular renin-angiotensin system in hypertensive subjects.
In vitro data indicate that the activation of A2 adenosine receptors increases renin release by the accumulation of cyclic AMP. Because in human forearm vessels beta-adrenergic receptor stimulation causes the local release of renin and angiotensin II through the increase of cyclic AMP, we evaluated in six essential hypertensive subjects whether adenosine can release vascular angiotensin II. Adenosine was infused into the brachial artery at cumulatively increasing doses (0.5, 1.5, and 5 micrograms/100 ml forearm tissue per minute for 5 minutes each) during saline infusion and in the presence of the adenosine antagonist theophylline (100 micrograms/100 ml forearm tissue per minute for 15 minutes), while venous (ipsilateral deep forearm vein) and arterial (brachial artery) angiotensin II (picograms per milliliter) were measured at the end of each infusion period, and forearm angiotensin II net balance (picograms per minute) was calculated by venous-arterial differences corrected for forearm blood flow (strain-gauge venous plethysmography) and hematocrit. In control conditions, adenosine, at higher doses, caused a dose-dependent vasodilation and increased venous angiotensin II without affecting arterial values; therefore, the calculated angiotensin II net balance showed an adenosine-mediated dose-dependent release. Theophylline pretreatment blunted adenosine-mediated forearm blood flow increments and angiotensin II release. The local origin of angiotensin II was further confirmed in another group of six hypertensive subjects in whom the angiotensin converting enzyme inhibitor captopril, locally infused at the rate of 2.5 micrograms/100 ml forearm tissue per minute for 15 minutes, abolished the adenosine-mediated venous angiotensin II increments. Our data indicate that exogenous adenosine can stimulate the production of angiotensin II in the forearm vessels of hypertensive patients.
Taddei
S
S
I Clinica Medica, University of Pisa, Italy.
Virdis
A
A
Favilla
S
S
Salvetti
A
A
D000241:Adenosine / Q000494:pharmacology*; D000328:Adult; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001160:Arterioles / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D002216:Captopril; D013806:Theophylline; D000241:Adenosine