Enalaprilat, losartan and LU 135252 in coronary blood flow regulation.
BACKGROUND
High plasma levels of angiotensin II are found in several pathologies such as hypertension, heart failure and myocardial infarction. The effect of high concentrations of angiotensin II on coronary circulation is not well defined. The aim of the present study was to assess coronary blood flow regulation during tachycardia in the presence of elevated coronary plasma levels of angiotensin II, and the changes induced by ACE inhibition and blockade of angiotensin II and endothelin-A receptors.


METHODS
Left anterior coronary artery was catheterized in 38 pigs to infuse the study drugs. Saline was infused for 15 min. Then, the first atrial pacing was performed. The pigs were distributed to: Group 1 (n = 7) angiotensin II; Group 2 (n = 7) enalaprilat + angiotensin II; Group 3 (n = 9) the bradykinin B2 antagonist HOE 140 + enalaprilat + angiotensin II; Group 4 (n = 7) losartan + angiotensin II; and Group 5 (n = 8) endothelin-A receptor antagonist LU 135252 + angiotensin II. After giving these infusions, a second pacing was repeated.


RESULTS
The increase in coronary blood flow induced by pacing with angiotensin II was reduced from 181 +/- 21% to 116 +/- 37% (P = 0.006 vs. saline). Enalaprilat, losartan and LU 135252 restored the capacity of coronary blood flow to increase during pacing (151 +/- 39%, 162 +/- 35% and 161 +/- 16%, respectively; P = NS, vs. saline), while HOE 140 abolished the effect of enalaprilat.


CONCLUSIONS
Moderately elevated coronary concentrations of angiotensin II reduced coronary blood flow during pacing. Enalaprilat, losartan and LU 135252 restored the hyperaemic coronary flow to similar values observed with saline. The beneficial effect of ACE inhibition is mediated through an increase in bradykinin.
Rigol
M
M
Institut de Malalties Cardiovasculars, IDIBAPS, Hospital Clínic, Barcelona, Spain. mrigol@clinic.ub.es
Heras
M
M
Solanes
N
N
Epelde
F
F
Roig
E
E
Pérez-Villa
F
F
Roqué
M
M
Sanz
G
G
D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D015773:Enalaprilat / Q000494:pharmacology*; D005260:Female; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D010666:Phenylpropionates / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D013552:Swine
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010666:Phenylpropionates; D011743:Pyrimidines; D000804:Angiotensin II; C107831:darusentan; C065679:icatibant; D015773:Enalaprilat; D019808:Losartan; D001920:Bradykinin