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Enalaprilat, losartan and LU 135252 in coronary blood flow regulation
1Institut de Malalties Cardiovasculars, IDIBAPS, Hospital Clínic, Barcelona, Spain. mrigol@clinic.ub.es
Insights
Elevated angiotensin II impairs coronary blood flow during tachycardia. ACE inhibition, losartan, and endothelin-A receptor blockade restored flow, with ACE inhibition
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- High angiotensin II levels are implicated in cardiovascular diseases like hypertension.
- The precise impact of elevated angiotensin II on coronary circulation, especially during increased heart rate, requires further elucidation.
Purpose of the Study:
- To investigate how elevated coronary angiotensin II affects coronary blood flow regulation during tachycardia.
- To evaluate the therapeutic potential of ACE inhibition, angiotensin II receptor blockade, and endothelin-A receptor antagonism in this context.
Main Methods:
- Pigs underwent catheterization of the left anterior coronary artery for drug infusion.
- Experimental groups received infusions of angiotensin II alone or in combination with enalaprilat, HOE 140 (bradykinin B2 antagonist), losartan, or LU 135252 (endothelin-A receptor antagonist).
- Coronary blood flow was measured during atrial pacing before and after infusions.
Main Results:
- Angiotensin II infusion significantly reduced the coronary blood flow increase during pacing.
- Enalaprilat, losartan, and LU 135252 administration restored the hyperemic response to pacing.
- The protective effect of enalaprilat was diminished by the bradykinin B2 antagonist HOE 140.
Conclusions:
- Moderately increased coronary angiotensin II levels impair coronary blood flow regulation during tachycardia.
- ACE inhibition, angiotensin II receptor blockade, and endothelin-A receptor blockade effectively restore coronary hyperemic capacity.
- The beneficial effects of ACE inhibition in this model are mediated by bradykinin.
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.
Design:
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.