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Angiotensin II-induced coronary and myocardial actions in the normal and the regionally ischemic dog heart
1 Mol Cell Cardiol 23 (Supplement V) (1991)
43 NORMALIZATION OF CARDIAC CATECHOLAMINE BALANCE DURING ISCHEMIA BY ENALAPRILAT.
EPIPHENOMENON OR BASIS FOR ITS ANTIISCHFMIC PROPERTIES? Wlllem I. Remme,Wares mdation, Rotterdam, The Netherlands. ACE-inhibition may limit myocardlal ischemia directly by reducing myocardialO2 demandand/or improvement of 02 supply and, indirectly, by modulating ischemla-induced neurolmmoral activation. To investigate whether &hernia-induced cardiac neurohmnoral activation is modulatedby enalaprllat Q. 12 fasting, untreated, normotensive pts with coronary artery diseaseunderwent 2 incremental pacing stresstests, 45 min before (Pl) and 15 min after 1.5 mg intravenous E (P2). E did not affect changesin double product (index of myocardialO2 demand),contractility, coronary flow and resistanceand myocardial 02 consumption. Nevertheless, it significantly reducedmyocardll ischemlawith diminished lactate production (myccardial lactate extraction -li9% (P2) vs -35~20%(Pl), 35%less ST-segmentdepressionand normalization of left ventricular filling pressurepost-pacing during P2 (al1p<.O5P2 vs Pl). Moreover, E markedly improved relaxation waul 10 (P2) vs Smsec(PI). p<.OS] and abolished the increase in arterial pressuresobserved during Pl. E prevented ischemla-induced neurohumoral activation [hnorepinephrine0.62 (P2) vs 1.7nmol (Pl) and&pkphrine 0.04 (P2) vs 0.26nmolll (Pl), both p<.O5]. Moreover, E reduced angiotensln II levels by 15%and modulated angiotensin II activation during pacing bangotensin II 0.52 (P2) vs 2.53pmoVl (Pl), p<.OS]. In addition, E prevented &hernia-induced cardiac catecholamineuptake bnorepinephrlne -0.03 I (P2) vs O.O8Sm0l/ti (Pl) and Aeplneptie -0.001 (P2) vs O.O23nmol/min(Pl), both pc.OS]. These data indicate that enalaprilat limits myocardial ischemiathrough a modulating effect on systemicand cardiac neurohumoralactivities, which may affect &hernia-induced systemicandcoronary vasoconstrlction.
44 CAPTOPRIL INFLUENCES SYMPATHETIC ACl’MTY IN MYOCARDILJTH Klaus Addicks, Dirk Happi+, Alexander Hess,Peter R&en. De artment of Anatomy, Umversi of Cologne,DSOOO Cologne 41 f o demonstrate the influence or Captopnl on sym athetic nerve fibres isolated rat hearts were perfusedAn ‘otensin I, II (lO-8m) or Captopn*P(10-6m) were added to the Intraaxonal catec!folamines of the sym athetlc nerve fibres were demonstrate flurescence microscopy and measured.6 issue catecholamineswere measured with The influence of Angiotensin or Captopril on coronary vessels was demonstrated by measuringflow of the effluate. control Ang.1 Ang.II Ang.1+ Capt catecholamme 1,41 1,68 1,77 1,so -intraaxonal area [%] 603 470 tissue-catechola.mine[ng/g] 562 710 102 flow in 35 min. [ml] 249 119 1he decreaseof catecholammefluorescencedemonstrates catecholamine releaseby sympatheticnerve fibres. Captopril suppressesthe Ang.-induced catecholaminerelease.
45
302
ANGIOTENSIN II-INDUCED CORONARY AND MYOCAROIAL ACTIONS IN THE NORMAL AND THE REGIONALLY ISCHEMIC DOG HEART. Violetta KBkesi, Tobias KBngeter, Miklds Tbth, Alexander JuhiiszNagy. Cardiovascular Surgical Clinic, Serrmelweis University, Budapest, Hungary The widespread usage of angiotensin-converting enzyme inhibitors as therapeutic agents has renewed interest in steady-state actions of angiotensin II (AI11 on the in situ heart. Systemic and local effects of AI1 on coronary blood flow and myocardial function of pentobarbital anesthetized open chest dogs (n=26) were investigated with standard hemodynamic methods in normal (A) and with computerized cardiothermography in regionally ischemic (LAD occluded) heartF (B). A: In normal hearts, only low doses of close arterial infusions of AI1 (25-50 ng/m?n ic) elicited coronary constriction. Large doses or systemic infusions (13-800 ng/kg/min iv) caused dose-dependent increases of coronary flow, ventricular force and myocardial 02 consumption with a parallel increase of the arterial pressure. The coronary responses were bidirectionally modulated by the adrenergic effects involved. 8: The regional blood supplies to the ischemic and nonischemic ventricular regions were elevated by systemic AII.The elevation was relatively large in the ischemic area at the medium, but blunted in all areas at high doses; while the preischemic regional-, and volume-flow dose-response curves run parallel. We concluded that intracoronary AI1 evokes slight and balanced constrictor responses in the coronary circulation. Systemic administrations exclusively increase the coronary flow. The significance of differences in elevations of the ischemic (collateral) and nonischemic blood flows in local myocardial ischemia needs further studies. s.19
43 NORMALIZATION OF CARDIAC CATECHOLAMINE BALANCE DURING ISCHEMIA BY ENALAPRILAT.
EPIPHENOMENON OR BASIS FOR ITS ANTIISCHFMIC PROPERTIES? Wlllem I. Remme,Wares mdation, Rotterdam, The Netherlands. ACE-inhibition may limit myocardlal ischemia directly by reducing myocardialO2 demandand/or improvement of 02 supply and, indirectly, by modulating ischemla-induced neurolmmoral activation. To investigate whether &hernia-induced cardiac neurohmnoral activation is modulatedby enalaprllat Q. 12 fasting, untreated, normotensive pts with coronary artery diseaseunderwent 2 incremental pacing stresstests, 45 min before (Pl) and 15 min after 1.5 mg intravenous E (P2). E did not affect changesin double product (index of myocardialO2 demand),contractility, coronary flow and resistanceand myocardial 02 consumption. Nevertheless, it significantly reducedmyocardll ischemlawith diminished lactate production (myccardial lactate extraction -li9% (P2) vs -35~20%(Pl), 35%less ST-segmentdepressionand normalization of left ventricular filling pressurepost-pacing during P2 (al1p<.O5P2 vs Pl). Moreover, E markedly improved relaxation waul 10 (P2) vs Smsec(PI). p<.OS] and abolished the increase in arterial pressuresobserved during Pl. E prevented ischemla-induced neurohumoral activation [hnorepinephrine0.62 (P2) vs 1.7nmol (Pl) and&pkphrine 0.04 (P2) vs 0.26nmolll (Pl), both p<.O5]. Moreover, E reduced angiotensln II levels by 15%and modulated angiotensin II activation during pacing bangotensin II 0.52 (P2) vs 2.53pmoVl (Pl), p<.OS]. In addition, E prevented &hernia-induced cardiac catecholamineuptake bnorepinephrlne -0.03 I (P2) vs O.O8Sm0l/ti (Pl) and Aeplneptie -0.001 (P2) vs O.O23nmol/min(Pl), both pc.OS]. These data indicate that enalaprilat limits myocardial ischemiathrough a modulating effect on systemicand cardiac neurohumoralactivities, which may affect &hernia-induced systemicandcoronary vasoconstrlction.
44 CAPTOPRIL INFLUENCES SYMPATHETIC ACl’MTY IN MYOCARDILJTH Klaus Addicks, Dirk Happi+, Alexander Hess,Peter R&en. De artment of Anatomy, Umversi of Cologne,DSOOO Cologne 41 f o demonstrate the influence or Captopnl on sym athetic nerve fibres isolated rat hearts were perfusedAn ‘otensin I, II (lO-8m) or Captopn*P(10-6m) were added to the Intraaxonal catec!folamines of the sym athetlc nerve fibres were demonstrate flurescence microscopy and measured.6 issue catecholamineswere measured with The influence of Angiotensin or Captopril on coronary vessels was demonstrated by measuringflow of the effluate. control Ang.1 Ang.II Ang.1+ Capt catecholamme 1,41 1,68 1,77 1,so -intraaxonal area [%] 603 470 tissue-catechola.mine[ng/g] 562 710 102 flow in 35 min. [ml] 249 119 1he decreaseof catecholammefluorescencedemonstrates catecholamine releaseby sympatheticnerve fibres. Captopril suppressesthe Ang.-induced catecholaminerelease.
45
302
ANGIOTENSIN II-INDUCED CORONARY AND MYOCAROIAL ACTIONS IN THE NORMAL AND THE REGIONALLY ISCHEMIC DOG HEART. Violetta KBkesi, Tobias KBngeter, Miklds Tbth, Alexander JuhiiszNagy. Cardiovascular Surgical Clinic, Serrmelweis University, Budapest, Hungary The widespread usage of angiotensin-converting enzyme inhibitors as therapeutic agents has renewed interest in steady-state actions of angiotensin II (AI11 on the in situ heart. Systemic and local effects of AI1 on coronary blood flow and myocardial function of pentobarbital anesthetized open chest dogs (n=26) were investigated with standard hemodynamic methods in normal (A) and with computerized cardiothermography in regionally ischemic (LAD occluded) heartF (B). A: In normal hearts, only low doses of close arterial infusions of AI1 (25-50 ng/m?n ic) elicited coronary constriction. Large doses or systemic infusions (13-800 ng/kg/min iv) caused dose-dependent increases of coronary flow, ventricular force and myocardial 02 consumption with a parallel increase of the arterial pressure. The coronary responses were bidirectionally modulated by the adrenergic effects involved. 8: The regional blood supplies to the ischemic and nonischemic ventricular regions were elevated by systemic AII.The elevation was relatively large in the ischemic area at the medium, but blunted in all areas at high doses; while the preischemic regional-, and volume-flow dose-response curves run parallel. We concluded that intracoronary AI1 evokes slight and balanced constrictor responses in the coronary circulation. Systemic administrations exclusively increase the coronary flow. The significance of differences in elevations of the ischemic (collateral) and nonischemic blood flows in local myocardial ischemia needs further studies. s.19