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Biphasic L-arginine uptake by isolated guinea pig heart
1 Mel
Cell
24
Cartliol
V) (1992)
(Supplement
Poster presentation: 8.30 - 17.50
October 1,1992 Coronary Circulation 27
QOES NITRIC OXIDE PLAY A ROLF IN COMPENSATORY CORONARY VASODILATATION? Agnes V6gh, James R. Parratt , L&l6 Szekeres, Julius Gy. Papp. ppartment of Pharmacology, A. Szent-GyBrgyi Medical University, Szeged, Hungary and Department of Physiology and Pharmacology, Strathclyde University, Glasgow, UK. It is well known that when one major branch of the left coronary artery is occluded there is a compensatory increase in blood flow in the other main branch and in its area of supply. In the present study we have examined whether the generation of nitric oxide (NO) IS concerned with this compensatory increase in coronary blopd flow (CBF) by using a selective inhibitor of the L-arginine NO pathway. In chloralose-urethane anaesthetized mongrel dogs the left anterior descending (LAD) and circumflex (LCX) coronary arteries were prepared for flow measurements using either electromagnetic or Doppler flow probes. Following the intravenous administration of nitro-L-arginine-methyl ester (L-NAME) in a dose of 10 mg kg-‘, occlusion of the LAD for 5 min resulted in a small reduction in diastolic blood pressure (frop 133 + 7 to 125 + 7 mmHg), an increase in LCX blood flow (from 37 +. 3 to 42 + 4 ml min- ) and in LVEDP (from 10 +. to 17 _+ 2 mmHg) and a redu ion in calculated coronary vascular resistance (from 4.0 + 0.4 to 3.3 + 0.3 mmHg/ml min- r ). These changes were similar to those observed in the absence of L-NAME. This suggests that NO plays no role in such an ischaemia-induced compensatory increase in CBF.
36
BIPHASIC L-AFWXNINE UPTAKE BY ISOLATED GUINEA PIG HEART Milosav M. Kostic. Gvozden L.HosiC and Mirko A. RosiC, University Kragujevac, Institute of Physiology, Faculty of Medicine, 34000 KraguJevac, Yugoslavia In order to evaluate the transport of L-arginine, the source of NO (EDHF), unidirectional transport was measured by rapid dual isotope dilution technique. The isolated guinea pig hearts werg retrogradely perfused with 3 ml/min Krebs-Hensel5it buffer (pH 7.41et37 1. After 30 min hearts were challenged with L- H-arginine and DC-mannitol (reference tracer) and coronary effluent was3collected sequentially for counting of radioactivity. The time course of H-arginine uptake showed two phases: the first (I) reached plateau after 9-15 s, whereas the second (II) developed plateau after
ca 20 s. Maximal 20 and 9.5 % in were calculated L-NAME (100 pM1, abolished maximal results indicate be endothelial (slow,low-affinity).
118
Effects
and net uptake was phase II, respectively.
(KmI=280 @l, KmII=350 PM; VmaxI=421, VmaxII=295 wol/min/g). competitive inhibitor of NO synthesis, almost completely uptake in phase I, but only about 20 % in phase II. Our two different compartments for uptake of arginine: one might (fast, high-affinity) and another one extraendothelial
of Leukotriene
myocardial
accounted to 33 and 23 % in phase I, but Two different values of Km and Vmax
D4
L-660,711
in isolated
Peter Gaudmn, Kai Hu, Georg ErU. Medizinische
Univ&t&sklinik
and
its specific
antagonist
rat
heart
after
infaction
Hong Han, Stefan
Neubauer,
Wiirzburg,
Germany
Coronary reserve is reduced in residual myocardium post myocardial infarction (Ml), and endogenous vasoconstrictors might be responsible for this functional disturbance. We studied the effects of leukotriene (LT) D4 and its novel Potent and selective antagonist L-600,711 (L). Rats were sham operated or the left coronary artery was ligated Permanently (perm) or for 3&nin or 6Omin followed by rqerfusion. Hearts were isolated and Perfused with KH-Buffer in the Langendorff mode 4 days (d), 4 weeks (w) or 8 w after Ml. Baseline coronary flow was 19.4ti.7 ml/mln in the sham ovated group and was unchanged after myocardial infaction. L-600,711 (0.6 pgg/min) had no effect on coronary flow and cardiac Performance. Coronary flow, left ventricular developed pressure, dp/dt and heart rate were dose-dependently reduced by LTD4 (12-240 ng/min) infusion. Dose-response curves for LTW on coronary flow were shifted to the left in rats with myocardial infarction over 4 w and were shifted to the right by L in all groups. The ED25 for LTD4 fmm all groups is shown in the table (meatis.e.m. * p-S.05 vs. sham). sham 30’4d 30’4w 60’4d 6(r4w perm,4d PemBw GouP ED25 34.ti3.02 32.7f2.99 23.8f2.57* 33.2t3.92 18.7f3.54* 30.1M.11 20.5f1.50’ ED25+L 133.9rt19.01 83.2f19.77 54.5k14.22’ 113.6zt24.0 6O.ti10.78* 121.ti4.14 98.92i31.31 ED25 was significantly reduced in rats with 30min or 6Omtn coronary occlusion followed by 4 w of reperfusion and 8 w of Permanent occlusion but unchanged in rats 4 d Post MLTbus, coronary constriction by LTD4 is enhanced in the chronic phase of myocardial infarction and attenuated by the specific LTD4 antagonist. s.51
Cell
24
Cartliol
V) (1992)
(Supplement
Poster presentation: 8.30 - 17.50
October 1,1992 Coronary Circulation 27
QOES NITRIC OXIDE PLAY A ROLF IN COMPENSATORY CORONARY VASODILATATION? Agnes V6gh, James R. Parratt , L&l6 Szekeres, Julius Gy. Papp. ppartment of Pharmacology, A. Szent-GyBrgyi Medical University, Szeged, Hungary and Department of Physiology and Pharmacology, Strathclyde University, Glasgow, UK. It is well known that when one major branch of the left coronary artery is occluded there is a compensatory increase in blood flow in the other main branch and in its area of supply. In the present study we have examined whether the generation of nitric oxide (NO) IS concerned with this compensatory increase in coronary blopd flow (CBF) by using a selective inhibitor of the L-arginine NO pathway. In chloralose-urethane anaesthetized mongrel dogs the left anterior descending (LAD) and circumflex (LCX) coronary arteries were prepared for flow measurements using either electromagnetic or Doppler flow probes. Following the intravenous administration of nitro-L-arginine-methyl ester (L-NAME) in a dose of 10 mg kg-‘, occlusion of the LAD for 5 min resulted in a small reduction in diastolic blood pressure (frop 133 + 7 to 125 + 7 mmHg), an increase in LCX blood flow (from 37 +. 3 to 42 + 4 ml min- ) and in LVEDP (from 10 +. to 17 _+ 2 mmHg) and a redu ion in calculated coronary vascular resistance (from 4.0 + 0.4 to 3.3 + 0.3 mmHg/ml min- r ). These changes were similar to those observed in the absence of L-NAME. This suggests that NO plays no role in such an ischaemia-induced compensatory increase in CBF.
36
BIPHASIC L-AFWXNINE UPTAKE BY ISOLATED GUINEA PIG HEART Milosav M. Kostic. Gvozden L.HosiC and Mirko A. RosiC, University Kragujevac, Institute of Physiology, Faculty of Medicine, 34000 KraguJevac, Yugoslavia In order to evaluate the transport of L-arginine, the source of NO (EDHF), unidirectional transport was measured by rapid dual isotope dilution technique. The isolated guinea pig hearts werg retrogradely perfused with 3 ml/min Krebs-Hensel5it buffer (pH 7.41et37 1. After 30 min hearts were challenged with L- H-arginine and DC-mannitol (reference tracer) and coronary effluent was3collected sequentially for counting of radioactivity. The time course of H-arginine uptake showed two phases: the first (I) reached plateau after 9-15 s, whereas the second (II) developed plateau after
ca 20 s. Maximal 20 and 9.5 % in were calculated L-NAME (100 pM1, abolished maximal results indicate be endothelial (slow,low-affinity).
118
Effects
and net uptake was phase II, respectively.
(KmI=280 @l, KmII=350 PM; VmaxI=421, VmaxII=295 wol/min/g). competitive inhibitor of NO synthesis, almost completely uptake in phase I, but only about 20 % in phase II. Our two different compartments for uptake of arginine: one might (fast, high-affinity) and another one extraendothelial
of Leukotriene
myocardial
accounted to 33 and 23 % in phase I, but Two different values of Km and Vmax
D4
L-660,711
in isolated
Peter Gaudmn, Kai Hu, Georg ErU. Medizinische
Univ&t&sklinik
and
its specific
antagonist
rat
heart
after
infaction
Hong Han, Stefan
Neubauer,
Wiirzburg,
Germany
Coronary reserve is reduced in residual myocardium post myocardial infarction (Ml), and endogenous vasoconstrictors might be responsible for this functional disturbance. We studied the effects of leukotriene (LT) D4 and its novel Potent and selective antagonist L-600,711 (L). Rats were sham operated or the left coronary artery was ligated Permanently (perm) or for 3&nin or 6Omin followed by rqerfusion. Hearts were isolated and Perfused with KH-Buffer in the Langendorff mode 4 days (d), 4 weeks (w) or 8 w after Ml. Baseline coronary flow was 19.4ti.7 ml/mln in the sham ovated group and was unchanged after myocardial infaction. L-600,711 (0.6 pgg/min) had no effect on coronary flow and cardiac Performance. Coronary flow, left ventricular developed pressure, dp/dt and heart rate were dose-dependently reduced by LTD4 (12-240 ng/min) infusion. Dose-response curves for LTW on coronary flow were shifted to the left in rats with myocardial infarction over 4 w and were shifted to the right by L in all groups. The ED25 for LTD4 fmm all groups is shown in the table (meatis.e.m. * p-S.05 vs. sham). sham 30’4d 30’4w 60’4d 6(r4w perm,4d PemBw GouP ED25 34.ti3.02 32.7f2.99 23.8f2.57* 33.2t3.92 18.7f3.54* 30.1M.11 20.5f1.50’ ED25+L 133.9rt19.01 83.2f19.77 54.5k14.22’ 113.6zt24.0 6O.ti10.78* 121.ti4.14 98.92i31.31 ED25 was significantly reduced in rats with 30min or 6Omtn coronary occlusion followed by 4 w of reperfusion and 8 w of Permanent occlusion but unchanged in rats 4 d Post MLTbus, coronary constriction by LTD4 is enhanced in the chronic phase of myocardial infarction and attenuated by the specific LTD4 antagonist. s.51