Prostacyclin, its fatty acid precursor and its metabolites on the inotropic function of and on the prostanoid generation by diabetic arteries
Relationships between arachidonic acid (AA) metabolism and contractile responses to Na arachidonate (NaA), to prostacyclin (PGI2) and to some of its metabolites, in mesenteric arteries, isolated from sham operated and from diabetic, totally pancreatectomized dogs, were studied. Arachidonate and pros...
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todo:paper_0232766X_v43_n8-9_pS257_SterinBorda2023-10-03T15:11:19Z Prostacyclin, its fatty acid precursor and its metabolites on the inotropic function of and on the prostanoid generation by diabetic arteries Sterin-Borda, L.J. Franchi, A.M. Borda, E.S. del Castillo, E. Gimeno, M.F. Gimeno, A.L. 6 oxoprostaglandin E1 6 oxoprostaglandin F1 alpha acetylsalicylic acid arachidonic acid arachidonic acid c 14 indometacin prostacyclin radioisotope tranylcypromine unclassified drug animal cell animal model artery article cardiovascular system diabetes mellitus dog drug efficacy endocrine system great blood vessel heart nonhuman peripheral vascular system priority journal 6-Ketoprostaglandin F1 alpha Alprostadil Animals Arachidonic Acid Arachidonic Acids Diabetes Mellitus, Experimental Dinoprostone Dogs Insulin Mesenteric Arteries Muscle Contraction Pancreatectomy Prostaglandins Prostaglandins E Vasoconstriction Animalia Canis familiaris Relationships between arachidonic acid (AA) metabolism and contractile responses to Na arachidonate (NaA), to prostacyclin (PGI2) and to some of its metabolites, in mesenteric arteries, isolated from sham operated and from diabetic, totally pancreatectomized dogs, were studied. Arachidonate and prostacyclin enhanced the resting basal tone of preparations from pancreatectomized animals but depressed it in vessels from intact normal controls or from sham operated dogs. Inhibitors of thromboxane A2 (TXA2) biosynthesis, abolished in vitro the vasoconstricting effect of NaA and PGI2 in diabetics; whereas inhibitors of PGI2 biosynthesis blocked the vasodilating influence of NaA in normal mesenterics. Additionally, antagonists of cyclooxygenase activity precluded both the vasoconstricting and vasodilating actions of NaA in normal and in diabetic arteries, respectively, as well as the PGI2 tone enhancement in vessels from diabetics. Blockers of adrenoreceptors and antagonists of lipoxygenases failed to block the positive inotropic effects of PGI2 in mesenterics from diabetic dogs. On the other hand, 6-keto-PGF(1α) did not evoke contractile influences, either in diabetics or in controls, whereas 6-keto-PGE1 induced, in both groups, a dose-dependent relaxation. In arteries from pancreatectomized animals treated with insulin, PGI2 induced a biphasic effect (constriction and relaxation) of magnitudes between those seen in normal controls or sham operated and in untreated diabetics. The basal radio-conversion of exogenous [1-14C]-AA, evidenced that mesenterics from diabetic animals generated more TXB2 than vessels from intact normal control or from sham-operated dogs. Moreover, in the presence of exogenous PGI2, the vascular production of TXB2 from AA in the diabetic group was significantly greater than that of preparations not exposed to PGI2. The % conversion of AA into PGI2 (assessed as 6-oxo-PGF(1α)) was similar in arteries from intact normal controls, from sham operated or from diabetic animals. Insulin given in vivo abolished the greater basal conversion of AA into TXB2 by mesenterics from diabetic dogs and attenuated significantly the enhanced prostacyclin-evoked generation of thromboxane. The present results strongly suggest that the normal tone enhancement evoked by NaA and by PGI2, in mesenteric arteries from diabetic dogs, is presumably related to the generation of TXA2 by vessel walls themselves. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_0232766X_v43_n8-9_pS257_SterinBorda |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
6 oxoprostaglandin E1 6 oxoprostaglandin F1 alpha acetylsalicylic acid arachidonic acid arachidonic acid c 14 indometacin prostacyclin radioisotope tranylcypromine unclassified drug animal cell animal model artery article cardiovascular system diabetes mellitus dog drug efficacy endocrine system great blood vessel heart nonhuman peripheral vascular system priority journal 6-Ketoprostaglandin F1 alpha Alprostadil Animals Arachidonic Acid Arachidonic Acids Diabetes Mellitus, Experimental Dinoprostone Dogs Insulin Mesenteric Arteries Muscle Contraction Pancreatectomy Prostaglandins Prostaglandins E Vasoconstriction Animalia Canis familiaris |
| spellingShingle |
6 oxoprostaglandin E1 6 oxoprostaglandin F1 alpha acetylsalicylic acid arachidonic acid arachidonic acid c 14 indometacin prostacyclin radioisotope tranylcypromine unclassified drug animal cell animal model artery article cardiovascular system diabetes mellitus dog drug efficacy endocrine system great blood vessel heart nonhuman peripheral vascular system priority journal 6-Ketoprostaglandin F1 alpha Alprostadil Animals Arachidonic Acid Arachidonic Acids Diabetes Mellitus, Experimental Dinoprostone Dogs Insulin Mesenteric Arteries Muscle Contraction Pancreatectomy Prostaglandins Prostaglandins E Vasoconstriction Animalia Canis familiaris Sterin-Borda, L.J. Franchi, A.M. Borda, E.S. del Castillo, E. Gimeno, M.F. Gimeno, A.L. Prostacyclin, its fatty acid precursor and its metabolites on the inotropic function of and on the prostanoid generation by diabetic arteries |
| topic_facet |
6 oxoprostaglandin E1 6 oxoprostaglandin F1 alpha acetylsalicylic acid arachidonic acid arachidonic acid c 14 indometacin prostacyclin radioisotope tranylcypromine unclassified drug animal cell animal model artery article cardiovascular system diabetes mellitus dog drug efficacy endocrine system great blood vessel heart nonhuman peripheral vascular system priority journal 6-Ketoprostaglandin F1 alpha Alprostadil Animals Arachidonic Acid Arachidonic Acids Diabetes Mellitus, Experimental Dinoprostone Dogs Insulin Mesenteric Arteries Muscle Contraction Pancreatectomy Prostaglandins Prostaglandins E Vasoconstriction Animalia Canis familiaris |
| description |
Relationships between arachidonic acid (AA) metabolism and contractile responses to Na arachidonate (NaA), to prostacyclin (PGI2) and to some of its metabolites, in mesenteric arteries, isolated from sham operated and from diabetic, totally pancreatectomized dogs, were studied. Arachidonate and prostacyclin enhanced the resting basal tone of preparations from pancreatectomized animals but depressed it in vessels from intact normal controls or from sham operated dogs. Inhibitors of thromboxane A2 (TXA2) biosynthesis, abolished in vitro the vasoconstricting effect of NaA and PGI2 in diabetics; whereas inhibitors of PGI2 biosynthesis blocked the vasodilating influence of NaA in normal mesenterics. Additionally, antagonists of cyclooxygenase activity precluded both the vasoconstricting and vasodilating actions of NaA in normal and in diabetic arteries, respectively, as well as the PGI2 tone enhancement in vessels from diabetics. Blockers of adrenoreceptors and antagonists of lipoxygenases failed to block the positive inotropic effects of PGI2 in mesenterics from diabetic dogs. On the other hand, 6-keto-PGF(1α) did not evoke contractile influences, either in diabetics or in controls, whereas 6-keto-PGE1 induced, in both groups, a dose-dependent relaxation. In arteries from pancreatectomized animals treated with insulin, PGI2 induced a biphasic effect (constriction and relaxation) of magnitudes between those seen in normal controls or sham operated and in untreated diabetics. The basal radio-conversion of exogenous [1-14C]-AA, evidenced that mesenterics from diabetic animals generated more TXB2 than vessels from intact normal control or from sham-operated dogs. Moreover, in the presence of exogenous PGI2, the vascular production of TXB2 from AA in the diabetic group was significantly greater than that of preparations not exposed to PGI2. The % conversion of AA into PGI2 (assessed as 6-oxo-PGF(1α)) was similar in arteries from intact normal controls, from sham operated or from diabetic animals. Insulin given in vivo abolished the greater basal conversion of AA into TXB2 by mesenterics from diabetic dogs and attenuated significantly the enhanced prostacyclin-evoked generation of thromboxane. The present results strongly suggest that the normal tone enhancement evoked by NaA and by PGI2, in mesenteric arteries from diabetic dogs, is presumably related to the generation of TXA2 by vessel walls themselves. |
| format |
JOUR |
| author |
Sterin-Borda, L.J. Franchi, A.M. Borda, E.S. del Castillo, E. Gimeno, M.F. Gimeno, A.L. |
| author_facet |
Sterin-Borda, L.J. Franchi, A.M. Borda, E.S. del Castillo, E. Gimeno, M.F. Gimeno, A.L. |
| author_sort |
Sterin-Borda, L.J. |
| title |
Prostacyclin, its fatty acid precursor and its metabolites on the inotropic function of and on the prostanoid generation by diabetic arteries |
| title_short |
Prostacyclin, its fatty acid precursor and its metabolites on the inotropic function of and on the prostanoid generation by diabetic arteries |
| title_full |
Prostacyclin, its fatty acid precursor and its metabolites on the inotropic function of and on the prostanoid generation by diabetic arteries |
| title_fullStr |
Prostacyclin, its fatty acid precursor and its metabolites on the inotropic function of and on the prostanoid generation by diabetic arteries |
| title_full_unstemmed |
Prostacyclin, its fatty acid precursor and its metabolites on the inotropic function of and on the prostanoid generation by diabetic arteries |
| title_sort |
prostacyclin, its fatty acid precursor and its metabolites on the inotropic function of and on the prostanoid generation by diabetic arteries |
| url |
http://hdl.handle.net/20.500.12110/paper_0232766X_v43_n8-9_pS257_SterinBorda |
| work_keys_str_mv |
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