Angiotensin subtype 1 blockade selectively potentiates adenosine subtype 2-mediated vasodilation.
A previous report demonstrated that infusion of adenosine into the forearm increased local vascular production of angiotensin II. We hypothesize that this increase in angiotensin II could attenuate the vasodilator response to adenosine subtype 2 (A2) receptor activation. The depressor and regional hemodynamic responses to the A2-selective adenosine agonist DPMA were measured in the presence and absence of angiotensin subtype 1 (AT1) receptor blockade (losartan, 10 mg/kg IV) in anesthetized rats. Losartan pretreatment (without versus with losartan) significantly potentiated DPMA-induced reductions in renal (-13 +/- 2% versus -22 +/- 4%, P < .05) and mesenteric (-11 +/- 2% versus -23 +/- 4%, P < .05) vascular resistances, resulting in a greater depressor response (-7 +/- 2 versus -18 +/- 3 mm Hg, P < .05). The decrease in hindquarter vascular resistance was not affected. To test the specificity of this interaction, we also evaluated nitroglycerin and nifedipine. Pretreatment with losartan had no effect on the responses to nitroglycerin, whereas the responses to nifedipine either were not affected or were attenuated (percent change in mesenteric vascular resistance: without losartan pretreatment, -30 +/- 1%; with losartan pretreatment, -24 +/- 2%, P < .05). To determine whether the decrease in arterial pressure after losartan pretreatment contributed to the potentiation of the DPMA-mediated effects, we infused nitroglycerin to lower mean arterial pressure comparably to losartan treatment. None of the hemodynamic responses to subsequent DPMA administration were affected. These data suggest that endogenous levels of angiotensin II, whether released locally or systemically, selectively attenuate the A2-mediated reductions in renal and mesenteric vascular resistances.
Smits
G J
GJ
Rhône-Poulenc Rorer Central Research, Collegeville, Pa. 19426-0107.
Kitzen
J M
JM
Perrone
M H
MH
Cox
B F
BF
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007275:Injections, Intravenous; D019808:Losartan; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; C056426:CGS 24012; D005996:Nitroglycerin; D009543:Nifedipine; D019808:Losartan; D000241:Adenosine