LOSARTAN PHARMACODYNAMICS PATHWAY (PW:0001464)
Description
Losartan is a selective and competitive non-peptide antagonist of angiotensin II receptor type 1 (Agtr1) used in the treatment of hypertension and heart failure. Angiotensin II (AngII) is one of several and probably the most potent peptide generated by the renin-angiotensin cascade. AngII signals through two receptor types to elicit distinct responses. The Agtr1 mediated pathway is involved in vasoconstriction, proliferation, hormone release and fluid homeostasis. The powerful but potentially harmful effects elicited by Agtr1 are counterbalanced by the Agtr2 mediated signaling. This pathway promotes vasodilation, NO release and growth inhibition. The Agtr1 mediated pathway is the better understood one. Losartan is one of eight Agrt1 antagonists collectively known as ARBs that are clinically available; losartan is the first marketed and the most frequently prescribed. ARBs are effective antihypertensive agents; however, they exhibit differences in terms of pharmacokinetics properties and pleiotropic effects. The losartan parent compound has a rather moderate affinity for the receptor. Following rapid absorption, losartan is metabolized to the more potent metabolite E3174 via the E3179 intermediate. The affinity of E3174 for the Agtr1 is 20- to 30-times greater than that of losartan. Other minor metabolites are also produced that are less active than the parent compound. . The Agtr1 receptor is a G-protein coupled receptor (GPCR) that couples to the Galphaq of heterotrimeric G proteins that activates phospholipase C; subsequent events lead to the activation of the protein kinase C (PKC) intracellular pathway. In the context of Agtr1, transactivation of epidermal growth factor/neuregulin and of Erk1/2 signaling as well as activation of the Jak-Stat pathway have been reported. Several amino acids have been identified as candidate components of the binding pocket of Agtr1. For losartan and probably E3174, these are serine 109, lysine 199 to a lesser extent, and asparagine 295 within transmembrane (TM) domains 3, 5 and 7 of the human receptor, respectively. These amino acids are conserved in the rat and mouse genes. In the crystal structure of the human receptor bound to its natural agonist, these positions are close to some of the positions the ligand uses and one position is identical. Given that the affinity of losartan (and other ARBs) matches the affinity of AngII, it is conceivable that the binding of antagonists interferes with the binding of the natural ligand. Losartan, in addition to its antihypertensive effects, may also slow down the progression of diabetic nephropathy, reduce renal disease progression in patients with type 2 diabetes (T2D) and decrease peripheral insulin resistance in T2D patients and animal models. Losartan also exhibits uricosuric action, possibly via inhibition of urate transporter 1, Slc22a12 known as URAT1 - one of several apical urate/anion exchangers involved in the reabsorption of urate in the proximal tubules. While some adverse side effects of ARBs have been reported, they are relatively rare.
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Pathway Diagram:
Genes in Pathway:
G
Ace
angiotensin I converting enzyme
ISO
SMPDB SMP:00162
NCBI chr10:91,410,129...91,430,246
G
Agt
angiotensinogen
ISO
SMPDB SMP:00162
NCBI chr19:69,426,540...69,447,017
G
Agtr1a
angiotensin II receptor, type 1a
TAS ISO
SMPDB PMID:23487168 SMP:00162, RGD:7364969
NCBI chr17:34,383,397...34,435,523
G
Ren
renin
ISO
SMPDB SMP:00162
NCBI chr13:47,348,312...47,359,539
Pathway Gene Annotations
Disease Annotations Associated with Genes in the losartan pharmacodynamics pathway
Ace abdominal aortic aneurysm , Acute Hepatitis , acute kidney failure , Acute Lung Injury , adenocarcinoma , adult respiratory distress syndrome , Albuminuria , alcohol-associated liver disease , alcoholic cardiomyopathy , allergic disease , allergic rhinitis , Alzheimer's disease , anemia , Angiotensin I-Converting Enzyme, Benign Serum Increase , ankylosing spondylitis , Arteriovenous Fistula , aspiration pneumonia , asthma , atrial fibrillation , autistic disorder , autosomal recessive polycystic kidney disease , Banti's Syndrome , Behcet's disease , berylliosis , bipolar disorder , brain ischemia , breast cancer , bronchiolitis obliterans , CAKUT , Cardiac Arrhythmias , Cardiomegaly , cardiovascular system disease , carotid artery disease , celiac disease , Cerebral Hemorrhage , cerebral infarction , Chemical and Drug Induced Liver Injury , chemical colitis , Chemotherapy-Induced Febrile Neutropenia , cholestasis , Chronic Hepatitis C , Chronic Intermittent Hypoxia , chronic myeloid leukemia , chronic obstructive pulmonary disease , coarctation of the aorta , congenital diaphragmatic hernia , Congenital Hepatic Fibrosis , congestive heart failure , coronary artery disease , Coronary Disease , coronary restenosis , Coronavirus infectious disease , Cough , COVID-19 , Cytomegalovirus Infections , diabetic angiopathy , Diabetic Cardiomyopathies , Diabetic Nephropathies , diabetic retinopathy , diastolic heart failure , diffuse cystic renal dysplasia , dilated cardiomyopathy , drug allergy , end stage renal disease , endomyocardial fibrosis , Endotoxemia , Experimental Arthritis , Experimental Colitis , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , extrinsic allergic alveolitis , Fabry disease , Familial Cerebral Cavernous Malformation , familial Mediterranean fever , Fetal Death , Fetal Growth Retardation , focal segmental glomerulosclerosis 1 , gallbladder adenocarcinoma , Gaucher's disease , genetic disease , Genetic Predisposition to Disease , glomerulonephritis , glomerulosclerosis , glycogen storage disease V , heart valve disease , Helicobacter Infections , hepatitis A , hepatocellular carcinoma , Hyperoxia , hypertension , Hypertensive Nephrosclerosis , hypertrophic cardiomyopathy , Hypotension , IgA glomerulonephritis , IgA vasculitis , in situ carcinoma , Insulin Resistance , intermediate coronary syndrome , Intestinal Reperfusion Injury , intracranial aneurysm , kidney disease , kidney failure , Kidney Reperfusion Injury , Left Ventricular Hypertrophy , leukemia , leukostasis , liver cirrhosis , Liver Metastasis , lung cancer , lung carcinoma , lung disease , Lung Injury , Lung Neoplasms , malaria , male infertility , Memory Disorders , Meningococcal Infections , metabolic dysfunction-associated steatotic liver disease , microcephaly , middle cerebral artery infarction , mitral valve disease , mitral valve prolapse , multiple myeloma , Mycobacterium Infections , myocardial infarction , myocarditis , Neoplasm Metastasis , nephritis , nephrosis , nephrotic syndrome , non-arteritic anterior ischemic optic neuropathy , obesity , obstructive sleep apnea , ocular hypotension , osteoporosis , Pain , pancreatic cancer , pancreatic ductal carcinoma , Parkinson's disease , Peritoneal Fibrosis , Pleural Effusion , pneumonia , polycythemia , pre-eclampsia , pre-malignant neoplasm , Pregnancy-Induced Hypertension , Premature Infant Diseases , Prenatal Exposure Delayed Effects , primary biliary cholangitis , Prostatic Neoplasms , proteinuria , pulmonary fibrosis , pulmonary hypertension , Puromycin Aminonucleoside Nephrosis , pyelonephritis , Radiation Nephropathy , renal fibrosis , Renal Tubular Dysgenesis , renovascular hypertension , Reperfusion Injury , respiratory system disease , Right Ventricular Hypertrophy , sarcoidosis , schizophrenia , Sepsis , severe acute respiratory syndrome , Staphylococcal Infections , stomach cancer , Stomach Neoplasms , stroke , subacute sclerosing panencephalitis , substance-induced psychosis , Sudden Death , systemic lupus erythematosus , systemic scleroderma , toxic shock syndrome , type 1 diabetes mellitus , type 2 diabetes mellitus , ureteral obstruction , uveitis , Vascular System Injuries , Venous Thromboembolism , Ventricular Fibrillation , Ventricular Remodeling , viral pneumonia , Weight Gain , Weight Loss Agt abdominal aortic aneurysm , Albuminuria , alcoholic cardiomyopathy , alcoholic hepatitis , Alkalosis , allergic disease , Alzheimer's disease , Anaphylaxis , anemia , Animal Disease Models , anti-basement membrane glomerulonephritis , anuria , aortic aneurysm , Aortic Calcification , atherosclerosis , atrial fibrillation , bipolar disorder , Bradycardia , breast cancer , Cardiac Arrhythmias , Cardiomegaly , cardiomyopathy , Cardiotoxicity , Cardiovascular Abnormalities , cardiovascular system disease , carotid artery disease , Catalepsy , cerebrovascular disease , Chemical and Drug Induced Liver Injury , cholestasis , Chronic Intermittent Hypoxia , chronic myeloid leukemia , cleidocranial dysplasia , coarctation of the aorta , cognitive disorder , congestive heart failure , corneal neovascularization , coronary artery disease , COVID-19 , Diabetic Cardiomyopathies , Diabetic Nephropathies , diabetic retinopathy , Diaphragmatic Hernia , diffuse scleroderma , dilated cardiomyopathy , Dissecting Aneurysm , Drug Overdose , end stage renal disease , endomyocardial fibrosis , essential hypertension , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Experimental Mammary Neoplasms , Fabry disease , Fetal Growth Retardation , Fibrosis , focal segmental glomerulosclerosis , gastric ulcer , genetic disease , glomerulonephritis , glucose intolerance , heart disease , Hemorrhage , hydronephrosis , Hyperalgesia , Hyperemia , hyperhomocysteinemia , hyperinsulinism , hypertension , Hypertensive Nephropathy , hypertrophic cardiomyopathy , Hypertrophy , hypokalemia , Hypotension , IgA glomerulonephritis , IgA vasculitis , impotence , Inflammation , inflammatory bowel disease , intermediate coronary syndrome , Intestinal Reperfusion Injury , kidney disease , kidney failure , left ventricular failure , Left Ventricular Hypertrophy , liver cirrhosis , malignant hypertension , meconium aspiration syndrome , Metabolic Syndrome , microcephaly , middle cerebral artery infarction , mitral valve prolapse , multiple sclerosis , myocardial infarction , Myocardial Ischemia , Myocardial Reperfusion Injury , Necrosis , Neointima , nephrosis , Neurobehavioral Manifestations , obesity , oligohydramnios , otosclerosis , Peptic Ulcer Hemorrhage , pneumonia , polycystic kidney disease , pre-eclampsia , prediabetes syndrome , Pregnancy-Induced Hypertension , Prenatal Exposure Delayed Effects , primary biliary cholangitis , proteinuria , pulmonary edema , pulmonary fibrosis , pulmonary hypertension , Puromycin Aminonucleoside Nephrosis , renal hypertension , Renal Tubular Dysgenesis , Reperfusion Injury , retinal vasculitis , retinopathy of prematurity , sciatic neuropathy , sick sinus syndrome , skin melanoma , stroke , Sudden Death , systemic scleroderma , temporal lobe epilepsy , thrombosis , transient cerebral ischemia , type 2 diabetes mellitus , ureteral obstruction , vascular disease , Vascular Malformations , Vascular Remodeling , Ventricular Remodeling Agtr1a abdominal aortic aneurysm , AIDS-Associated Nephropathy , Alveolar Bone Loss , Alzheimer's disease , anti-basement membrane glomerulonephritis , asthma , atrial fibrillation , breast cancer , breast lobular carcinoma , Cardiac Arrhythmias , Cardiomegaly , carotid artery disease , Carotid Artery Injuries , cerebrovascular disease , Chronic Intermittent Hypoxia , chronic kidney disease , congestive heart failure , corneal neovascularization , coronary artery disease , Coronary Disease , COVID-19 , Diabetic Nephropathies , diabetic retinopathy , Diaphragmatic Hernia , diffuse cystic renal dysplasia , dilated cardiomyopathy , Disorders of Environmental Origin , Ductal Carcinoma , essential hypertension , Experimental Liver Cirrhosis , Experimental Mammary Neoplasms , Experimental Radiation Injuries , Fetal Growth Retardation , Fibrosis , focal segmental glomerulosclerosis , Friedreich ataxia , genetic disease , glomerulosclerosis , glucose intolerance , Huntington's disease , hyperinsulinism , hypertension , Hypertensive Nephropathy , IgA glomerulonephritis , Inflammation , intermediate coronary syndrome , kidney disease , Left Ventricular Hypertrophy , limb ischemia , lung disease , Metabolic Syndrome , myocardial infarction , Myocardial Reperfusion Injury , Neoplasm Metastasis , nephritis , pancreatic ductal carcinoma , Parkinson's disease , patent ductus arteriosus , Pituitary Neoplasms , placental insufficiency , Postoperative Cognitive Dysfunction , Prenatal Exposure Delayed Effects , proteinuria , pulmonary fibrosis , pulmonary hypertension , renal cell carcinoma , renal hypertension , Renal Tubular Dysgenesis , renovascular hypertension , sarcoidosis , Spontaneous Abortions , Vascular System Injuries , Ventricular Remodeling , vesicoureteral reflux Ren acute kidney failure , Albuminuria , anemia , atrial fibrillation , autosomal dominant tubulointerstitial kidney disease 4 , Azotemia , Bartter disease , Cardiomegaly , chronic fatigue syndrome , Chronic Intermittent Hypoxia , colitis , congenital adrenal hyperplasia , congestive heart failure , Critical Illness , depressive disorder , Diabetic Nephropathies , Drug-Related Side Effects and Adverse Reactions , Endotoxemia , essential hypertension , Experimental Diabetes Mellitus , Fetal Growth Retardation , Fibrosis , genetic disease , hand, foot and mouth disease , Hemorrhage , hepatoblastoma , human cytomegalovirus infection , hypertension , Hyponatremia , Hypotension , ischemia , kidney disease , kidney failure , Left Ventricular Hypertrophy , Liddle syndrome , liver cirrhosis , malignant hypertension , metabolic dysfunction and alcohol associated liver disease , myocardial infarction , nephrosis , nephrotic syndrome , obesity , osteoporosis , periodontal disease , portal hypertension , Preeclamptic Toxemia , Prenatal Exposure Delayed Effects , primary biliary cholangitis , primary hyperaldosteronism , proteinuria , psoriasis , Puromycin Aminonucleoside Nephrosis , Renal Tubular Dysgenesis , renovascular hypertension , Retina Reperfusion Injury , Tonne-Kalscheuer syndrome , toxic shock syndrome , withdrawal disorder
abdominal aortic aneurysm Ace , Agt , Agtr1a Acute Hepatitis Ace acute kidney failure Ace , Ren Acute Lung Injury Ace adenocarcinoma Ace adult respiratory distress syndrome Ace AIDS-Associated Nephropathy Agtr1a Albuminuria Ace , Agt , Ren alcohol-associated liver disease Ace alcoholic cardiomyopathy Ace , Agt alcoholic hepatitis Agt Alkalosis Agt allergic disease Ace , Agt allergic rhinitis Ace Alveolar Bone Loss Agtr1a Alzheimer's disease Ace , Agt , Agtr1a Anaphylaxis Agt anemia Ace , Agt , Ren Angiotensin I-Converting Enzyme, Benign Serum Increase Ace Animal Disease Models Agt ankylosing spondylitis Ace anti-basement membrane glomerulonephritis Agt , Agtr1a anuria Agt aortic aneurysm Agt Aortic Calcification Agt Arteriovenous Fistula Ace aspiration pneumonia Ace asthma Ace , Agtr1a atherosclerosis Agt atrial fibrillation Ace , Agt , Agtr1a , Ren autistic disorder Ace autosomal dominant tubulointerstitial kidney disease 4 Ren autosomal recessive polycystic kidney disease Ace Azotemia Ren Banti's Syndrome Ace Bartter disease Ren Behcet's disease Ace berylliosis Ace bipolar disorder Ace , Agt Bradycardia Agt brain ischemia Ace breast cancer Ace , Agt , Agtr1a breast lobular carcinoma Agtr1a bronchiolitis obliterans Ace CAKUT Ace Cardiac Arrhythmias Ace , Agt , Agtr1a Cardiomegaly Ace , Agt , Agtr1a , Ren cardiomyopathy Agt Cardiotoxicity Agt Cardiovascular Abnormalities Agt cardiovascular system disease Ace , Agt carotid artery disease Ace , Agt , Agtr1a Carotid Artery Injuries Agtr1a Catalepsy Agt celiac disease Ace Cerebral Hemorrhage Ace cerebral infarction Ace cerebrovascular disease Agt , Agtr1a Chemical and Drug Induced Liver Injury Ace , Agt chemical colitis Ace Chemotherapy-Induced Febrile Neutropenia Ace cholestasis Ace , Agt chronic fatigue syndrome Ren Chronic Hepatitis C Ace Chronic Intermittent Hypoxia Ace , Agt , Agtr1a , Ren chronic kidney disease Agtr1a chronic myeloid leukemia Ace , Agt chronic obstructive pulmonary disease Ace cleidocranial dysplasia Agt coarctation of the aorta Ace , Agt cognitive disorder Agt colitis Ren congenital adrenal hyperplasia Ren congenital diaphragmatic hernia Ace Congenital Hepatic Fibrosis Ace congestive heart failure Ace , Agt , Agtr1a , Ren corneal neovascularization Agt , Agtr1a coronary artery disease Ace , Agt , Agtr1a Coronary Disease Ace , Agtr1a coronary restenosis Ace Coronavirus infectious disease Ace Cough Ace COVID-19 Ace , Agt , Agtr1a Critical Illness Ren Cytomegalovirus Infections Ace depressive disorder Ren diabetic angiopathy Ace Diabetic Cardiomyopathies Ace , Agt Diabetic Nephropathies Ace , Agt , Agtr1a , Ren diabetic retinopathy Ace , Agt , Agtr1a Diaphragmatic Hernia Agt , Agtr1a diastolic heart failure Ace diffuse cystic renal dysplasia Ace , Agtr1a diffuse scleroderma Agt dilated cardiomyopathy Ace , Agt , Agtr1a Disorders of Environmental Origin Agtr1a Dissecting Aneurysm Agt drug allergy Ace Drug Overdose Agt Drug-Related Side Effects and Adverse Reactions Ren Ductal Carcinoma Agtr1a end stage renal disease Ace , Agt endomyocardial fibrosis Ace , Agt Endotoxemia Ace , Ren essential hypertension Agt , Agtr1a , Ren Experimental Arthritis Ace Experimental Colitis Ace Experimental Diabetes Mellitus Ace , Agt , Ren Experimental Liver Cirrhosis Ace , Agt , Agtr1a Experimental Mammary Neoplasms Agt , Agtr1a Experimental Radiation Injuries Agtr1a extrinsic allergic alveolitis Ace Fabry disease Ace , Agt Familial Cerebral Cavernous Malformation Ace familial Mediterranean fever Ace Fetal Death Ace Fetal Growth Retardation Ace , Agt , Agtr1a , Ren Fibrosis Agt , Agtr1a , Ren focal segmental glomerulosclerosis Agt , Agtr1a focal segmental glomerulosclerosis 1 Ace Friedreich ataxia Agtr1a gallbladder adenocarcinoma Ace gastric ulcer Agt Gaucher's disease Ace genetic disease Ace , Agt , Agtr1a , Ren Genetic Predisposition to Disease Ace glomerulonephritis Ace , Agt glomerulosclerosis Ace , Agtr1a glucose intolerance Agt , Agtr1a glycogen storage disease V Ace hand, foot and mouth disease Ren heart disease Agt heart valve disease Ace Helicobacter Infections Ace Hemorrhage Agt , Ren hepatitis A Ace hepatoblastoma Ren hepatocellular carcinoma Ace human cytomegalovirus infection Ren Huntington's disease Agtr1a hydronephrosis Agt Hyperalgesia Agt Hyperemia Agt hyperhomocysteinemia Agt hyperinsulinism Agt , Agtr1a Hyperoxia Ace hypertension Ace , Agt , Agtr1a , Ren Hypertensive Nephropathy Agt , Agtr1a Hypertensive Nephrosclerosis Ace hypertrophic cardiomyopathy Ace , Agt Hypertrophy Agt hypokalemia Agt Hyponatremia Ren Hypotension Ace , Agt , Ren IgA glomerulonephritis Ace , Agt , Agtr1a IgA vasculitis Ace , Agt impotence Agt in situ carcinoma Ace Inflammation Agt , Agtr1a inflammatory bowel disease Agt Insulin Resistance Ace intermediate coronary syndrome Ace , Agt , Agtr1a Intestinal Reperfusion Injury Ace , Agt intracranial aneurysm Ace ischemia Ren kidney disease Ace , Agt , Agtr1a , Ren kidney failure Ace , Agt , Ren Kidney Reperfusion Injury Ace left ventricular failure Agt Left Ventricular Hypertrophy Ace , Agt , Agtr1a , Ren leukemia Ace leukostasis Ace Liddle syndrome Ren limb ischemia Agtr1a liver cirrhosis Ace , Agt , Ren Liver Metastasis Ace lung cancer Ace lung carcinoma Ace lung disease Ace , Agtr1a Lung Injury Ace Lung Neoplasms Ace malaria Ace male infertility Ace malignant hypertension Agt , Ren meconium aspiration syndrome Agt Memory Disorders Ace Meningococcal Infections Ace metabolic dysfunction and alcohol associated liver disease Ren metabolic dysfunction-associated steatotic liver disease Ace Metabolic Syndrome Agt , Agtr1a microcephaly Ace , Agt middle cerebral artery infarction Ace , Agt mitral valve disease Ace mitral valve prolapse Ace , Agt multiple myeloma Ace multiple sclerosis Agt Mycobacterium Infections Ace myocardial infarction Ace , Agt , Agtr1a , Ren Myocardial Ischemia Agt Myocardial Reperfusion Injury Agt , Agtr1a myocarditis Ace Necrosis Agt Neointima Agt Neoplasm Metastasis Ace , Agtr1a nephritis Ace , Agtr1a nephrosis Ace , Agt , Ren nephrotic syndrome Ace , Ren Neurobehavioral Manifestations Agt non-arteritic anterior ischemic optic neuropathy Ace obesity Ace , Agt , Ren obstructive sleep apnea Ace ocular hypotension Ace oligohydramnios Agt osteoporosis Ace , Ren otosclerosis Agt Pain Ace pancreatic cancer Ace pancreatic ductal carcinoma Ace , Agtr1a Parkinson's disease Ace , Agtr1a patent ductus arteriosus Agtr1a Peptic Ulcer Hemorrhage Agt periodontal disease Ren Peritoneal Fibrosis Ace Pituitary Neoplasms Agtr1a placental insufficiency Agtr1a Pleural Effusion Ace pneumonia Ace , Agt polycystic kidney disease Agt polycythemia Ace portal hypertension Ren Postoperative Cognitive Dysfunction Agtr1a pre-eclampsia Ace , Agt pre-malignant neoplasm Ace prediabetes syndrome Agt Preeclamptic Toxemia Ren Pregnancy-Induced Hypertension Ace , Agt Premature Infant Diseases Ace Prenatal Exposure Delayed Effects Ace , Agt , Agtr1a , Ren primary biliary cholangitis Ace , Agt , Ren primary hyperaldosteronism Ren Prostatic Neoplasms Ace proteinuria Ace , Agt , Agtr1a , Ren psoriasis Ren pulmonary edema Agt pulmonary fibrosis Ace , Agt , Agtr1a pulmonary hypertension Ace , Agt , Agtr1a Puromycin Aminonucleoside Nephrosis Ace , Agt , Ren pyelonephritis Ace Radiation Nephropathy Ace renal cell carcinoma Agtr1a renal fibrosis Ace renal hypertension Agt , Agtr1a Renal Tubular Dysgenesis Ace , Agt , Agtr1a , Ren renovascular hypertension Ace , Agtr1a , Ren Reperfusion Injury Ace , Agt respiratory system disease Ace Retina Reperfusion Injury Ren retinal vasculitis Agt retinopathy of prematurity Agt Right Ventricular Hypertrophy Ace sarcoidosis Ace , Agtr1a schizophrenia Ace sciatic neuropathy Agt Sepsis Ace severe acute respiratory syndrome Ace sick sinus syndrome Agt skin melanoma Agt Spontaneous Abortions Agtr1a Staphylococcal Infections Ace stomach cancer Ace Stomach Neoplasms Ace stroke Ace , Agt subacute sclerosing panencephalitis Ace substance-induced psychosis Ace Sudden Death Ace , Agt systemic lupus erythematosus Ace systemic scleroderma Ace , Agt temporal lobe epilepsy Agt thrombosis Agt Tonne-Kalscheuer syndrome Ren toxic shock syndrome Ace , Ren transient cerebral ischemia Agt type 1 diabetes mellitus Ace type 2 diabetes mellitus Ace , Agt ureteral obstruction Ace , Agt uveitis Ace vascular disease Agt Vascular Malformations Agt Vascular Remodeling Agt Vascular System Injuries Ace , Agtr1a Venous Thromboembolism Ace Ventricular Fibrillation Ace Ventricular Remodeling Ace , Agt , Agtr1a vesicoureteral reflux Agtr1a viral pneumonia Ace Weight Gain Ace Weight Loss Ace withdrawal disorder Ren
