Alleles of the inducible nitric oxide synthase locus (Nos2) cosegregated highly significantly (P < 0.0001) with blood pressure in an F2 population [F2(S x MNS), n = 171] derived from a cross of inbred Dahl salt-sensitive (S) rats with Milan normotensive rats (MNS). In contrast, alleles at the constitutive brain nitric oxide synthase locus (Nos1) did not cosegregate with blood pressure in several F2 populations. Nos2 was mapped on rat chromosome 10. Nine genetic markers, including the angiotensin-converting enzyme (Ace) and Nos2 loci spanning roughly 46 cM on rat chromosome 10, all cosegregated strongly with blood pressure in the F2(S x MNS) population. Nos2 showed the highest LOD score of 6.3. Ace and Nos2 are 30 cM apart. In an F2 population [F2(S x WKY), n = 159] derived from a cross of S rats with Wistar-Kyoto (WKY) rats, Nos2 alleles did (P = 0.0070), but Ace alleles did not (P = 0.91), cosegregate with blood pressure. We conclude that the Nos2 locus rather than the Nos1 locus is a candidate for influencing blood pressure in the S rat. There are probably two separate but linked quantitative trait loci (QTL) for blood pressure on rat chromosome 10, one marked by Ace and the other marked by Nos2. In F2(S x MNS) functionally variant alleles at both QTL influence blood pressure, but in F2(S x WKY) only the QTL marked by Nos2 is segregating alleles influencing blood pressure.
A Y Deng, J P Rapp
Title and authors | Publication | Year |
---|---|---|
Shifting Paradigm from Gene Expressions to Pathways Reveals Physiological Mechanisms in Blood Pressure Control in Causation
Deng AY, Menard A, Deng DW |
International journal of molecular sciences | 2023 |
Nitric oxide and salt resistance in Dahl rats: no role of inducible NO synthase.
Zicha J, Řezáčová L, Vaněčková I |
2022 | |
Towards Precision Medicine for Hypertension: A Review of Genomic, Epigenomic, and Microbiomic Effects on Blood Pressure in Experimental Rat Models and Humans
S Padmanabhan, B Joe |
Physiological reviews | 2017 |
Melatonin prevents kidney injury in a high salt diet-induced hypertension model by decreasing oxidative stress
A Leibowitz, A Volkov, K Voloshin, C Shemesh, I Barshack, E Grossman |
Journal of Pineal Research | 2015 |
High-intensity interval training attenuates endothelial dysfunction in a Dahl salt-sensitive rat model of heart failure with preserved ejection fraction
V Adams, M Alves, T Fischer, N Rolim, S Werner, N Schütt, TS Bowen, A Linke, G Schuler, U Wisloff |
Journal of applied physiology | 2015 |
African Americans, hypertension and the renin angiotensin system
SF Williams |
World journal of cardiology | 2014 |
eLS
YC Chang, YH Yu, LM Chuang |
Encyclopedia of Life Sciences | 2013 |
Role of Rac1 GTPase in salt-sensitive hypertension:
M Nagase |
Current Opinion in Nephrology and Hypertension | 2013 |
Age-Dependent Salt Hypertension in Dahl Rats: Fifty Years of Research
J Zicha, Z Dobešová, M Vokurková, H Rauchová, S Hojná, M Kadlecová, M Behuliak, I Vaněčková, J Kuneš |
Physiological research / Academia Scientiarum Bohemoslovaca | 2012 |
Preventive Cardiology: Companion to Braunwald's Heart Disease
PN Hopkins |
Preventive Cardiology: Companion to Braunwald's Heart Disease | 2011 |
Mitochondrial polymorphisms in rat genetic models of hypertension
S Kumarasamy, K Gopalakrishnan, A Shafton, J Nixon, J Thangavel, P Farms, B Joe |
Mammalian Genome | 2010 |
CELLULAR EXPRESSION OF RENAL, CARDIAC AND PULMONARY INDUCIBLE NITRIC OXIDE SYNTHASE IN DOUBLE-TRANSGENIC MICE EXPRESSING HUMAN RENIN AND ANGIOTENSINOGEN GENES
ZA Radi, Y Murad |
Clinical and Experimental Pharmacology and Physiology | 2009 |
Renal functional, not morphological, abnormalities account for salt sensitivity in Dahl rats
WM Manger, S Simchon, MB Stokes, JJ Reidy, AR Kumar, L Baer, G Gallo, FJ Haddy |
Journal of Hypertension | 2009 |
Submegabase resolution of epistatically interacting quantitative trait loci for blood pressure applicable for essential hypertension
C Chauvet, S Charron, A Ménard, C Xiao, J Roy, AY Deng |
Journal of Hypertension | 2008 |
Sexual Dimorphism on Hypertension of Quantitative Trait Loci Entrapped in Dahl Congenic Rats
AY Deng, A Ménard, C Xiao, J Roy |
Clinical and Experimental Hypertension | 2008 |
Fine-mapping and comprehensive transcript analysis reveals nonsynonymous variants within a novel 1.17 Mb blood pressure QTL region on rat chromosome 10
Y Saad, MR Garrett, E Manickavasagam, S Yerga-Woolwine, P Farms, T Radecki, B Joe |
Genomics | 2007 |
The Monocyte Chemotactic Protein-1 Gene May Contribute to Hypertension in Dahl Salt-Sensitive Rats
N YASUI, K KAJIMOTO, T SUMIYA, T OKUDA, N IWAI |
Hypertension Research | 2007 |
Individual QTLs controlling quantitative variation in blood pressure inherited in a Mendelian mode
C Duong, S Charron, Y Deng, C Xiao, A Ménard, J Roy, AY Deng |
Heredity | 2006 |
Functional significance of single nucleotide polymorphisms within the 5′-flanking region of β2-adrenergic receptor gene
H Wu, W Tang, H Li, X Zhou, Y Yang, H Yu, K Li, C Xiao, AY Deng |
Journal of Hypertension | 2006 |
Principles of Molecular Medicine
MS Runge, C Patterson |
2006 | |
The Vascular Endothelium II
S Moncada, A Higgs |
2006 | |
Antioxidative effect of p38 mitogen-activated protein kinase inhibitor in the kidney of hypertensive rat
A Tojo, ML Onozato, N Kobayashi, A Goto, H Matsuoka, T Fujita |
Journal of Hypertension | 2005 |
Antioxidative effect of p38 mitogen-activated protein kinase inhibitor in the kidney of hypertensive rat:
A Tojo, ML Onozato, N Kobayashi, A Goto, H Matsuoka, T Fujita |
Journal of Hypertension | 2005 |
Effects of chronic inhibition of inducible nitric oxide synthase in hyperthyroid rats
I Rodríguez-Gómez, R Wangensteen, JM Moreno, V Chamorro, A Osuna, F Vargas |
American journal of physiology. Endocrinology and metabolism | 2005 |
Pathogenesis of Hypertension in African Americans
S Nesbitt, RG Victor |
Congestive Heart Failure | 2004 |
Genetic Factors Underlying Impaired Endothelium-Dependent Vasorelaxation in the Stroke-Prone Spontaneously Hypertensive Rat
B Gigante, S Rubattu, R Stanzione, A Lombardi, M Schiavoni, D Tarasi, M Volpe |
High Blood Pressure & Cardiovascular Prevention | 2003 |
Human Chromosome 17 in Essential Hypertension
J Knight, PB Munroe, JC Pembroke, MJ Caulfield |
Annals of Human Genetics | 2003 |
Downregulation of nitric oxide synthase in nephrotic syndrome: role of proteinuria
Z Ni, ND Vaziri |
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2003 |
Cardiovascular and renal control in NOS-deficient mouse models
PA Ortiz, JL Garvin |
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology | 2003 |
Mechanisms of salt-sensitive hypertension: role of renal medullary inducible nitric oxide synthase
N Tian, AW Gannon, RA Khalil, RD Manning |
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology | 2003 |
Oral administration of L-arginine decreases blood pressure and increases renal excretion of sodium and water in renovascular hypertensive rats
SA Gouvêa, MR Moysés, NS Bissoli, JG Pires, AM Cabral, GR Abreu |
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] | 2003 |
The Role of ACE2 in Cardiovascular Physiology
GY Oudit, MA Crackower, PH Backx, JM Penninger |
Trends in Cardiovascular Medicine | 2003 |
Inducible nitric oxide synthase and cardiac dysfunction in salt-sensitive hypertension
LF Arnolda |
Journal of Hypertension | 2002 |
The altered balance between sympathetic nervous system and nitric oxide in salt hypertensive Dahl rats: ontogenetic and F2 hybrid studies
Z Dobešová, J Kuneš, J Zicha |
Journal of Hypertension | 2002 |
Accelerated congenics for mapping two blood pressure quantitative trait loci on chromosome 10 of Dahl rats
Z Sivo, B Malo, J Dutil, AY Deng |
Journal of Hypertension | 2002 |
Inhibition of inducible nitric oxide synthase during high dietary salt intake
J Bloch, C Qiu, A Erdely, C Baylis |
American Journal of Hypertension | 2002 |
Mapping baroreceptor function to genome: a mathematical modeling approach
CM Kendziorski, AW Cowley, AS Greene, HC Salgado, HJ Jacob, PJ Tonellato |
Genetics | 2002 |
1A-779 attenuates angiotensin-(1–7) depressor response in salt-induced hypertensive rats
MA Bayorh, D Eatman, M Walton, RR Socci, M Thierry-Palmer, N Emmett |
Peptides | 2002 |
Renal medullary nitric oxide deficit of Dahl S rats enhances hypertensive actions of angiotensin II
M Szentiványi, AP Zou, DL Mattson, P Soares, C Moreno, RJ Roman, AW Cowley |
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology | 2002 |
Two linked blood pressure quantitative trait loci on chromosome 10 defined by dahl rat congenic strains
MR Garrett, X Zhang, OI Dukhanina, AY Deng, JP Rapp |
Hypertension | 2001 |
Salt-Sensitive Hypertension and Inducible Nitric Oxide Synthase: Form-Function Dichotomy of a Coding Region Mutation, Mutatis Mutandis
J Loscalzo |
Circulation research | 2001 |
Renal cyclic 3′,5′-guanosine monophosphate and sodium excretion in Dahl salt-resistant and Dahl salt-sensitive rats
LJ Millatt, HM Siragy |
Journal of Hypertension | 2000 |
Tubulointerstitial injury and loss of nitric oxide synthases parallel the development of hypertension in the Dahl-SS Rat
RJ Johnson, KL Gordon, C Giachelli, T Kurth, MM Skelton, AW Cowley |
Journal of Hypertension | 2000 |
The Laboratory Rat
H Schulz, H Muhle |
The Laboratory Rat | 2000 |
Molecular aspects of soluble guanylyl cyclase regulation
S Andreopoulos, A Papapetropoulos |
General Pharmacology: The Vascular System | 2000 |
Genetic Analysis of Inherited Hypertension in the Rat
JP Rapp |
Physiological reviews | 2000 |
Genetically defined risk of salt sensitivity in an intercross of Brown Norway and Dahl S rats
AW Cowley, M Stoll, AS Greene, ML Kaldunski, RJ Roman, PJ Tonellato, NJ Schork, P Dumas, HJ Jacob |
Physiological genomics | 2000 |
Mechanisms of salt-sensitive hypertension: role of inducible nitric oxide synthase
DY Tan, S Meng, GW Cason, RD Manning |
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology | 2000 |
Blood pressure QTL that differentiate Dahl salt-sensitive and spontaneously hypertensive rats
MR Garrett, Y Saad, H Dene, JP Rapp |
Physiological genomics | 2000 |
Genes and Hypertension: From Gene Mapping in Experimental Models to Vascular Gene Transfer Strategies
AF Dominiczak, DC Negrin, JS Clark, MJ Brosnan, MW McBride, MY Alexander |
Hypertension | 2000 |
Dysfunctional Renal Nitric Oxide Synthase as a Determinant of Salt-Sensitive Hypertension: Mechanisms of Renal Artery Endothelial Dysfunction and Role of Endothelin for Vascular Hypertrophy and Glomerulosclerosis
M Barton, I Vos, S Shaw, P Boer, LI D'uscio, HJ Gröne, TJ Rabelink, T Lattmann, P Moreau, TF Lüscher |
Journal of the American Society of Nephrology : JASN | 2000 |
Enhanced Nitric Oxide Synthesis Reverses Salt-Induced Alterations in Blood Flow and Cgmp Levels
MA Bayorh, E Williams, M Thierry-Palmer, G Sanford, N Emmett, S Harris-Hooker, RR Socci, TC Chu |
Clinical and Experimental Hypertension | 1999 |
GENETIC ANALYSIS IN DAHL SALT-SENSITIVE RATS
N Kato |
Clinical and Experimental Pharmacology and Physiology | 1999 |
Fluxes and metabolic pools as model traits for quantitative genetics. I. The L-shaped distribution of gene effects
B Bost, C Dillmann, D Vienne |
Genetics | 1999 |
Report on rat chromosome 10
M Knoblauch, H Jacob, D Ganten, K Lindpaintner |
Journal of Experimental Animal Science | 1999 |
Ontogenetic Aspects of Hypertension Development: Analysis in the Rat
J Zicha, J Kuneš |
Physiological reviews | 1999 |
Handling 22 NaCl by the Blood-Brain Barrier and Kidney: Its Relevance to Salt-Induced Hypertension in Dahl Rats
S Simchon, W Manger, E Golanov, J Kamen, G Sommer, CH Marshall |
Hypertension | 1999 |
Fluxes and Metabolic Pools as Model Traits for Quantitative Genetics. I. The L-Shaped Distribution of Gene Effects
B Bost, C Dillmann, D de Vienne |
Genetics | 1999 |
Is the nitric oxide system involved in genetic hypertension in Dahl rats?
AY Deng |
Kidney International | 1998 |
Linkage mapping of rat chromosome markers generated from chromosome-sorted DNA
AY Deng, WH Smith-Mensah, B Hoebee, M Garrett, JP Rapp |
Mammalian Genome | 1998 |
In search of hypertension genes in Dahl salt-sensitive rats
AY Deng |
Journal of Hypertension | 1998 |
Hypertension
P Hamet, Z Pausova, V Adarichev, K Adaricheva, J Tremblay |
Journal of Hypertension | 1998 |
Possible Mechanisms of Salt-Induced Hypertension in Dahl Salt-Sensitive Rats
MA Bayorh, EC Ogbolu, E Williams, M Thierry-Palmer, G Sanford, N Emmett, S Harris-Hooker, RR Socci, TC Chu, VM Chenault |
Physiology & Behavior | 1998 |
A primer on the genetics of hypertension
D Cusi, G Bianchi |
Kidney International | 1998 |
Genetic basis of salt-susceptibility in the Sabra rat model of hypertension
Y Yagil, C Yagil |
Kidney International | 1998 |
Molecular Analysis of the Rat Inducible Nitric Oxide Synthase Genes
AY Deng |
Clinical and Experimental Hypertension | 1998 |
Genetics of experimental hypertension
AF Dominiczak, JS Clark, B Jeffs, NH Anderson, CD Negrin, WK Lee, MJ Brosnan |
Journal of Hypertension | 1998 |
Genetic mapping of soluble guanylyl cyclase genes: implications for linkage to blood pressure in the Dahl rat
M Azam, G Gupta, W Chen, S Wellington, D Warburton, RS Danziger |
Hypertension | 1998 |
Genome scan and congenic strains for blood pressure QTL using Dahl salt-sensitive rats
MR Garrett, H Dene, R Walder, QY Zhang, GT Cicila, S Assadnia, AY Deng, JP Rapp |
Genome research | 1998 |
Renal medullary interstitial infusion of l -arginine prevents hypertension in Dahl salt-sensitive rats
N Miyata, AP Zou, DL Mattson, AW Cowley |
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology | 1998 |
Candidate Genes in the Regulation of Na + Transport by Inner Medullary Collecting Duct Cells From Dahl Rats
RF Husted, JP Rapp, JB Stokes |
Hypertension | 1998 |
Vascular Smooth Muscle Nitric Oxide Synthase Anomalies in Dahl/Rapp Salt-Sensitive Rats
PY Chen, RD Gladish, PW Sanders |
Hypertension | 1998 |
Inducible Nitric Oxide Synthase and Blood Pressure
DL Mattson, CY Maeda, TD Bachman, AW Cowley |
Hypertension | 1998 |
Concordant Genetic and Physiological Data Are Required for Candidate Genes
JP Rapp |
Hypertension | 1998 |
Salt Susceptibility Maps to Chromosomes 1 and 17 With Sex Specificity in the Sabra Rat Model of Hypertension
C Yagil, M Sapojnikov, R Kreutz, G Katni, K Lindpaintner, D Ganten, Y Yagil |
Hypertension | 1998 |
Resistance to Endotoxin Shock in Spontaneously Hypertensive Rats
C Bernard, R Merval, B Esposito, A Tedgui |
Hypertension | 1998 |
Salt Wars
C Lenfant |
Science | 1998 |
Hypertension and the Insulin Resistance Syndrome of Rats
I Klimeš, E Šeböková |
Annals of the New York Academy of Sciences | 1997 |
Linkage map and congenic strains to localize blood pressure QTL on rat Chromosome 10
OI Dukhanina, H Dene, AY Deng, CR Choi, B Hoebee, JP Rapp |
Mammalian Genome | 1997 |
Novel Quantitative Trait Loci for Blood Pressure and Related Traits on Rat Chromosomes 1, 10, and 18
P Kovács, B Voigt, I Klöting |
Biochemical and Biophysical Research Communications | 1997 |
Genetic Susceptibility for Human Familial Essential Hypertension in a Region of Homology with Blood Pressure Linkage on Rat Chromosome 10
C Julier, M Delepine, B Keavney, J Terwilliger, S Davis, DE Weeks, T Bui, X Jeunemaitre, G Velho, P Froguel, P Ratcliffe, P Corvol, F Soubrier, GM Lathrop |
Human Molecular Genetics | 1997 |
Hypertension and the Insulin Resistance Syndrome of Rats.: Are They Related?
I Klimeš, E Šeböková |
Annals of the New York Academy of Sciences | 1997 |
Nitric Oxide Synthase and Renin-Angiotensin System Gene Expression in Salt-Sensitive and Salt-Resistant Sabra Rats
A Lippoldt, V Gross, K Schneider, A Hansson, S Nadaud, W Schneider, M Bader, C Yagil, Y Yagil, FC Luft |
Hypertension | 1997 |
Congenic Strains for the Blood Pressure Quantitative Trait Locus on Rat Chromosome 2
AY Deng, H Dene, JP Rapp |
Hypertension | 1997 |
Absence of Linkage for ‘Endothelial’ Nitric Oxide Synthase Locus to Blood Pressure in Dahl Rats
AY Deng, JP Rapp |
Hypertension | 1997 |
Endothelial Function in Hypertension
D Webb, P Vallance |
1997 | |
Genetic mapping of two blood pressure quantitative trait loci on rat chromosome 1
L Gu, H Dene, AY Deng, B Hoebee, MT Bihoreau, M James, JP Rapp |
Journal of Clinical Investigation | 1996 |
Salt-sensitive hypertension: Lessons from animal models1
PW Sanders |
American Journal of Kidney Diseases | 1996 |
COSEGREGATION OF THE NEW REGION ON CHROMOSOME 3 WITH SALT-INDUCED HYPERTENSION IN FEMALE F2 PROGENY FROM STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS
C Matsumoto, Y Nara, K Ikeda, T Tamada, T Mashimo, T Nabika, M Sawamura, Y Yamori |
Clinical and Experimental Pharmacology and Physiology | 1996 |
Localization of the gene responsible for the op (osteopetrotic) defect in rats on chromosome 10
EF Remmers, Y Du, YP Ding, S Kotake, L Ge, H Zha, EA Goldmuntz, RL Wilder, C Hansen |
Journal of Bone and Mineral Research | 1996 |
EXAMINATION OF THE ROLE OF NITRIC OXIDE SYNTHASE AND RENAL KALLIKREIN AS CANDIDATE GENES FOR ESSENTIAL HYPERTENSION
LR Friend, BJ Morris, PT Gaffney, LR Griffiths |
Clinical and Experimental Pharmacology and Physiology | 1996 |
Inducible nitric oxide synthase in the cardiovascular system
K Bhagat, P Vallance |
Heart (British Cardiac Society) | 1996 |
Impaired Renal Vasodilation and Urinary cGMP Excretion in Dahl Salt-Sensitive Rats
S Simchon, W Manger, G Blumberg, J Brensilver, S Cortell |
Hypertension | 1996 |
Role of 20-HETE in Elevating Loop Chloride Reabsorption in Dahl SS/Jr Rats
AP Zou, HA Drummond, RJ Roman |
Hypertension | 1996 |
Nitric oxide as a vascular modulator
GN Welch, GR Upchurch, J Loscalzo |
Blood Reviews | 1995 |
Nitric Oxide and Vascular Disease
J Loscalzo |
New England Journal of Medicine | 1995 |
Nitric Oxide Synthase Isoform Activities in Kidney of Dahl Salt-Sensitive Rats
Y Ikeda, K Saito, JI Kim, M Yokoyama |
Hypertension | 1995 |
Linkage mapping of the neuronal nitric oxide synthase gene (Nos1) to rat Chromosome 12
AY Deng, JP Rapp, H Kato, MT Bihoreau |
Mammalian Genome | 1995 |