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INDEX A mechanisms of action, 245, 246 nonaromatizable androgens, 242 suppression of androgen studies, 237, 238, 240 replacement therapy in men, bioavailability offorms, 236, 237 patches, 237 structure, 236 synthesis, 235 ANG II, see Angiotensin II Angiotensin converting enzyme (ACE) inhibitors, cardioprotection via kinins, heart failure, 147-153 left ventricular hypertrophy reduction, 142-144 left ventricular remodeling following myocardial damage, 145-147 myocardial ischemic preconditioning, 144, 145 overview, 137, 138 kinins in antihypertensive effect, 141, 142 Angiotensin II (ANG II), cardiac effects, direct actions, chronotropic/arrhythmogenic actions, 57 contractile/inotropic actions, 56 oxidative actions, 58, 59, 62 thrombogenic actions, 57, 58 trophic/mitogenic actions, 55, 56 indirect effects, congestive heart failure, 61 hypertension, 60, 61, 105 ischemia, 60 myocardial infarction, 60 vasoconstriction, 59, 60 circulating versus locally generated protein, 54,55 half-life, 53 induction of aldosterone synthesis, 74, 75 plasma renin activity in measurement, 54 receptors, 55, 56, 58, 148, 150, 151, 153 regulation of eicosanoid synthesis, 199 ANP, see Atrial natriuretic peptide Apoptosis, atrial natriuretic peptide induction, 14 nitric oxide induction, 186 AA, see Arachidonic acid ABR, see Arterial baroreflex ACE inhibitors, see Angiotensin converting enzyme inhibitors Acetylcholine (ACh), estrogen replacement therapy effects on response, 223, 224 half-life, 85, 86 nitric oxide release stimulation, 223 regulation of eicosanoid synthesis, 197, 198 suppression of release, neuropeptide Y, 90-92, 95, 96, 98 norepinephrine, 90-92, 95, 96, 98 ACh, see Acetylcholine ACTH, see Adrenocorticotrophic hormone Adrenocorticotrophic hormone (ACTH), induction of aldosterone synthesis, 7 urocortin secretion induction, 48 Adrenomedullin (AM), discovery, 21 effects, adrenal cortex, 27,32 animal versus human models, 25, 26 central nervous system, 29-31 heart, 28,32 kidney, 27 lung, 28, 29 pituitary gland, 31, 32 vasculature, 26, 27 gene, regulation of expression, 23 structure, 21, 22 processing, 22 receptors and signal transduction, 24, 25 tissue distribution, 23 Aldosterone, see Mineralocorticoids AM, see Adrenomedullin Androgens, degradation, 235-237, 243 nonlipid risk factors for coronary artery disease, 246 plasma lipid effects, clinical significance, 246 delayed puberty patients, 240 epidemiological studies, 237 exogenous testosterone, 241, 242 hypogonadalmen, 240, 241 253 Index 254 Arachidonic acid (AA), release pathways, 195, 196 Arginine vasopressin (AVP), basal blood pressure contribution, 104, 105 cardiac output regulation, 105 hypertension role, 105-108 interaction with arterial and cardiopulmonary reflexes, 108-110 receptors, 107, 110 secretion regulation, 103 vasoconstriction, 103, 105, 108 Arrhythmias, angiotensin II actions, 57 eicosanoid role, 205, 206 Arterial baroreflex (ABR), arginine vasopressin interaction with arterial and cardiopulmonary reflexes, 108110 basal blood pressure regulation, 104 regulation of arginine vasopressin, 103 Atherosclerosis, eicosanoid role, 207, 208 endothelin role in remodeling, 166, 167 Atrial natriuretic peptide (ANP), activation of expression, phenylephrine, 6-8 physical factors, 8, 9 protein kinase C, 6 Ras, 7, 12 antimitogenic activity, 14 apoptosis induction, 14 cardiac expression, heart failure, 11 hypertrophy, 9-13 myocardial infarction, 11 normal heart, 3,4 discovery, 1 eicosanoid effects on expression, 202 gene, regulation of expression, 4--9 structure, 2, 3 processing, 1-3 receptors, 13-15 transgenic mice, knockout effects, 15 overexpression effects, 15 receptors, 15, 16 A VP, see Arginine vasopressin B B type natriuretic peptide (BNP), antimitogenic activity, 14 cardiac expression, heart failure, 11 hypertrophy, 9-11 myocardial infarction, 11 normalheart,3,4,6 gene, regulation of expression, 6, 9 structure, 2, 3 processing, 3 receptors, 13, 14 transgenic mice, 15 BNP, see B type natriuretic peptide Bradykinin, see Kinins C C type natriuretic peptide (CNP), antimitogenic activity, 14 cardiac expression, 3, 4 gene,2,3 processing, 3 receptors, 13, 14 Cardiac hypertrophy, aldosteronism induction, 69, 70, 72 angiotensin II role, 55, 56 cardiprotection by kinins and ACE inhibitors, 142-144 culture models, 10 eicosanoid role, 208 etiology, 9,10 natriuretic peptide expression, early gene response in regulation, 11, 12 kinase cascades, 12, 13 markers, 11 Rafpathwayactivation, 12 Ras pathway activation, 12 temporal gene expression, 10, 11 Camitine palmitoyltransferase (CPT-I), insulin effects, 127, 128 Catecholamines, see Dopamine; Epinephrine; Norepinephrine CBF, see Cerebral blood flow Cerebral blood flow (CBF), adrenomedullin effects, 29 CNP, see C type natriuretic peptide Congestive heart failure, see Heart failure Corticotropin-releasing factor (CRF), cardiovascular actions, 41, 42 receptors, distribution, 39,40 urocortin binding, 40, 41, 46 stress response, 39 CPT -I, see Camitine palmitoyltransferase CRF, see Corticotropin-releasing factor D Dexamethasone, see Glucocorticoids Dihydroxytestosterone, see Androgens Dopamine, sources in heart, 81 Index E Eicosanoids, arachidonic acid metabolism, 195, 196 cardiac effects, adrenergic transmission, 200 atrial natriuretic peptide, effects on expression, 202 bradykinin modulation, 202 cholinergic transmission, 201 coronary circulation, 201, 202 ion channels, 202, 203 norepinephrine release inhibition, 200 overview, 199,208,209 reflexogenic effects, 201 disease role, arrhythmias, 205, 206 atherosclerosis, 207, 208 cardiac hypertrophy, 208 congestive heart failure, 206, 207 myocardial ischemia/reperfusion, 203-205 synthesis in heart, effects, acetylcholine, 197, 198 angiotensin II, 199 calcium, 198 humoral agents, 199 norepinephrine, 197, 198 overview, 197 Endothelin (ET), cardiac endothelin, contractile activity, 163 hypertrophy induction, 163 receptors, 162, 163 release, 162 processing, 159 receptors, 161, 162 role in cardiac disease, congestive heart failure, 164, 165 myocardial ischemia, 165, 166 remodeling during atherosclerosis and angioplasty-induced restenosis, 166, 167 snake venom sarafotoxins, 159 types and structures, 159 Epinephrine, sources in heart, 81 Estrogen, cardioprotection, overview of mechanisms, 220 deficiency and cardiovascular disease, 227, 228 endothelial cell function effects, 222- 225 males, effects on plasma lipid profile, cardiovascular benefits, 244, 245, 247 estradiol functions, 242, 243 lipoprotein (a) levels, 243, 244 myocardium effects, 226, 227 255 nongenomic effects on cardiovascular system, 222 receptors, binding sites, 221 tissue distribution, 220 types, 221 replacement therapy effects in women, blood flow, 225 carbohydrate metabolism, 227 cardiac performance, 226, 227 coagulation system, 227 endothelial cell acetylcholine response, 223,224 lipid profiles, 227 lipoprotein (a) levels, 227 myocardial infarction rate, 219, 228--230 progestin combination therapy, 229, 230 vascular vasomotor tone and blood flow effects, 225 ET, see Endothelin F Fatty acid metabolism, insulin effects, 118, 119, 121, 127, 128 G Glucocorticoids, diovascular effects, 73 mineralocorticoid receptor binding, 70, 71 receptors, 73 synthesis, 74 Glucose transport, insulin effects, 121-124 Glycogen metabolism, insulin effects, 126, 127 Glycolysis, insulin effects, 124 H Heart failure, adrenomedullin therapy, 28 angiotensin II role, 61 atrial natriuretic peptide expression, 11 cardiprotection by kinins and ACE inhibitors, 147-153 eicosanoid role, 206, 207 endothelin role, 164, 165 nitric oxide role, apoptosis induction, 186 metabolic substrate utilization changes, 185, 187 production of nitric oxide, 183-185 spironolactone therapy, 73 Heart rate (HR), arginine vasopressin regulation, 105 response to sympathetic neural activity, 84, 85 Index 256 sympathetic--parasympathetic interactions in regulation, 88, 89, 93, 94 High-density lipoprotein, see Lipid profiles HR, see Heart rate Hydroxyeicosatetraenoic acids, see Eicosanoids II b-Hydroxysteroid dehydrogenase, mineralocorticoid receptor occupancy regulation,71 types, 71 Hypertension, aldosteronism induction, 69, 70, 72, 73 angiotensin II role, 60, 61, 105 arginine vasopressin role, 105-108 glucocorticoid induction, 73 Hypertrophy, see Cardiac hypertrophy I Insulin, actions on heart, contractile and ion transport protein regulation, 116, 117 estrogen replacement therapy effects on carbohydrate metabolism, 227 fatty acid metabolism, 118, 119, 121, 127, 128 glucose transport, 121-124 glycogen metabolism, 126, 127 glycolysis, 124 mechanical function of cardiac muscle, 115, 116 metabolic enzyme responses, overview, 120, 121 perfusion effects, 117, 118 protein metabolism, 118 pyruvate dehydrogenase complex, 124-126 signaling overview, 121 K Kinins, cardioprotection, heart failure, 147-153 left ventricular hypertrophy reduction, 142-144 left ventricular remodeling following myocardial damage, 145-147 myocardial ischemic preconditioning, 144, 145 overview, 137, 138 eicosanoid modulation of cardiac effects, 202 hypertension pathogenesis role, 140, 141 kallikrein processing, 137, 138, 140 kininases, angiotensin converting enzyme, see Angiotensin converting enzyme synthesis, 140 types, 137, 138 receptors, antagonists and cardioprotection, 140, 142, 143, 148, 150-152 signaling, 139 types, 138, 139 L Left ventricular hypertrophy, see Cardiac hypertrophy Leukotrienes, see Eicosanoids Lipid profiles, aging effects, 237 androgen effects, clinical significance, 246 delayed puberty patients, 240 epidemiological studies, 237 exogenous testosterone, 241, 242 hypogonadalmen, 240, 241 mechanisms of action, 245, 246 nonaromatizable androgens, 242 suppression of androgen studies, 237, 238, 240 estrogen therapy effects, men, cardiovascular benefits, 244, 245, 247 estradiol functions, 242, 243 lipoprotein (a) levels, 243, 244 women, 227 Lipoprotein (a), androgen suppression effects in men, 238, 240 estrogen therapy effect on levels, females, 227 males, 243, 244 Lipoprotein lipase (LPL), insulin effects, 127129 Low-density lipoprotein, see Lipid profiles LPL, see Lipoprotein lipase M MI, see Myocardial infarction Mineralocorticoids, aldosterone, heart factor synthesis, 74, 75 heart metabolism, 75 induction by angiotensin II, 74, 75 cardiac hypertrophy induction, 69, 70, 72, 73 cardiac output effects, 69 hypertension induction, 69, 70, 72, 73 inotropic effects, 71, 72 receptors, 70, 71 second messenger effects, 72 synthesis, 74 Myocardial infarction (MI), angiotensin II role, 60 Index 257 estrogen replacement therapy effects, 219, 228-230 natriuretic peptide expression, 11 Myocardial ischemia, angiotensin II role, 60 cardiprotection by kinins and ACE inhibitors, left ventricular remodeling following myocardial damage, 145-147 preconditioning, 144, 145 eicosanoid role, 203-205 endothelin role, 165, 166 removal, 82, 83 sources in heart, 81, 82 sympathetic-parasympathetic interactions in heart regulation, autonomic excitation sequence, 91-98 cardiac cycle length, 98 heart rate control, 88, 89, 93, 94 postjunctional mechanisms, 89, 90 prejunctional mechanisms, 90, 91 toxic effects, 86 NPY, see Neuropeptide Y N o Natriuretic peptides, see Atrial natriuretic peptide; B type natriuretic peptide; C type natriuretic peptide NE, see Norepinephrine Neuropeptide Y (NPY), acetylcholine suppression, 90--93, 95, 96, 98 vagal neurotransmission role, 91-93 Nitric oxide (NO), blood flow and resistance regulation, coronary regulation, 179-182 periphery regulation, 178, 179 diffusibility, 177, 178 enzyme regulation, 177 estrogen effects on release, 223 exercise response and cardiac function, 187 heart failure, apoptosis induction, 186 metabolic substrate utilization changes, 185,187 production of nitric oxide, 183-185 negative inotropic effects, 186, 187 overview ofparacrine functions, 175 oxidative metabolism regulation, 182, 183 synthases, regulation, 176, 177 types, 175, 176 NO, see Nitric oxide Norepinephrine (NE), acetylcholine suppression of release, 90--92, 95,96,98 cardiac response to sympathetic neural activity, atrioventricular conduction, 84 contraction, 84 heart rate, 84, 85 kinetics of decay, 86-88 kinetics of onset, 84-86 eicosanoids, inhibition of release, 200 regulation of synthesis, 197, 198 exchange in cardiac interstitium, release, 83 Oxidative damage, angiotensin II role, 58, 59, 62 P PAl-I, see Plasminogen activator inhibitor type-l PDC, see Pyruvate dehydrogenase complex Plasminogen activator inhibitor type-l (PAI-I), induction by renin-angiotensin system, 57, 58 Prostaglandins, see Eicosanoids Pyruvate dehydrogenase complex (PDC), insulin effects, 124-126 R Renin-angiotensin system, angiotensin II actions, see Angiotensin II basal blood pressure contribution, 104 overview, 53, 54 Restenosis, endothelin role in remodeling, 166, 167 S Sauvagine, cardiovascula~ actions, 41, 42 SNS, see Sympathetic nervous system Sympathetic nervous system (SNS), basal blood pressure contribution, 104 cardiac response to sympathetic neural activity, atrioventricular conduction, 84 contraction, 84 heart rate, 84, 85 kinetics of decay, 86-88 kinetics of onset, 84-86 parasympathetic interactions in heart regulation, autonomic excitation sequence, 91-98 cardiac cycle length, 98 heart rate control, 88, 89, 93, 94 postjunctional mechanisms, 89, 90 prejunctional mechanisms, 90, 91 258 Index appetite suppression, 48, 49 autonomic blockade studies, 46----48 cardiac contractility, 45 coronary vasodilation, 45, 46 hypotension, 42, 45 inotropic actions, 42, 45, 46, 49 receptors, 40, 41, 46 stress response, 48, 49 structure, 40 tissue distribution, 40, 41 Urotensin, cardiovascular actions, 41, 42 T Testosterone, see Androgens u Ucn, see Urocortin Urocortin (Ucn), adrenocorticotrophic hormone secretion induction,48 v Vasopressin, see Arginine vasopressin