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Expression of the renin-angiotensin system (RAS) in metanephric organ culture: evidence of an avascular RAS
AJH-APRIL1996-VOL. 9, NO.4, PART 2
ORALS: ainical Genetics
Friday, May 17, 11:30 am
Friday, May 17, 11:45 am
OBESITY GENE IS NOT LINKED WITH BODY MASS INDEX NOR ESSENTIAL HYPERTENSION IN AFRICAN AMERICAN SIBLINGS. M. Heur, M.P. Rutkowski", C. Klanke, Y.R. Su, V. Carter", M.e. Reif", A. Menon. University of Cncinnatl College of Medicine, Cncinnatl, OH. The human homologue of the obesity gene (Ob) has recently been identified (Nature 1994;372:425-432). We analyzed linkage In moderately obese, African American siblings with essential hypertension using locus 0751875, a tightly linked polymorphism (Genome Research 1995;5:5-12). We studied 147 hypertensive African Americans in 67 sibships. 98 were female, 49 male. Mean age was 50 ± 11 (sd). Mean body mass Index (BMI) was 32.3 ± 7 kg/mI. Mean systolic and diastolic pressures were 145 ± 19 and 92 ± 13 at a mean of 1.7 anti-hypertensive medications. Heterozygosity score of this polymorphic marker was 0.90. The Sibpal subroutine of S.AG.E. was used to analyze the data (U.S.P.H.S. Resource grant 1 P41 RR03655). Sibling pair linkage analysis using the log transformation of BMI as the quantitative trait showed:
EFFECT 0' DIETAIlY SODIUM (NA, ON VIlINAIlY 6-BETA. BYDROXYCORTISOL EXCRETION IN SALT-SENS111VE (SS) AND SALT-RESISTANT (SJl) ADOLESCENT AFRICANAMERICANS. 1M..IJg0. DK W1IJoII, L Kramer, CO Wetllnll!On,
Trait Locus d.f. BMI Db
66
Mean Shared Alleles full sibs half sibs 0.43 0.18
Tvalue .(J.93
Pvalue 0.18
(lnteroopt- 0.10, Slope - -.031)
Affected sibling pair linkage analysis to determine linkage with the phenotype of essential hypertension showed: Estimated Alleles Identical By Descent TPfull sibs half sibs value value • pain mean ad • pain mean ad 73 0.43 0.34 5 0.17 0.24 -1.9 1.00 In conclusion, we could not demonstrate linkage with the phenotype of moderate obesity nor essential hypertension in African American hypertensive sibling pairs. However, we cannot exclude linkage In Individuals with more severe obesity. Key Words:
Obesity, Genetics, Essential Hypertension, Human, AfrIcan Americans
Modical Collea' of VIrIlIl1.. RIchmond, VJraInJa. Cor\llOl 00 II tbt aubsll'ate for family 3A cytochrome P~ enzyme (CYP3A) conYenloa to 6&-hydrol)'eortllol (68-00-1). Urtnary 68-00·F/l'n. , nUo II a propc»ed Indell of In mo CYP3A IlCtIvlty. PnllmlnU'1 lIudl_ haw au..-ted tbt pNence of an tncn.ed nlIo In ••ubset of Mrlcan-Amertcan _tlal hyperteDllwa. Con'eIatIona bdween l'IIIaI CYP3A IClMty and bloocl Pl'llaun (BP) with \'II'18tIoa In .....1raIn IIIId drvl treatment In tbt spontaneous Iy hypen-Ive nt .... aIao consillentwltb • role of CYP3A In tbt pal!lopella of BP elevation In thll .netlc modeL W. ha.......uated tbt urlnU'1 elCl'etIon of 68-00-' In a
prevlo...ly charac:tertzed aubset of ICIoIeacent normotensl.. MrlcanAmerkanI determined to be SS or SR. A~ta __ d.sItled • SS If their mean BP Increued >5 mm 01 !'rom • 5 day low N.+ diet (50 mEqJ24hr) to • 10 day hlp Na+ diet (NaCl .upp'-at -150 mEqJ24hr). 68-00-' _ m_ured by ny absorbance oa _ .... ph_ BPLC with pre-atractloa or lII'Int oa two CII1rtdl_ (reYene IIIId normal ph-. sequentially) and II reported • IlCIfU 1m.
Pkl
SS (n-l4)
Iel!!: 115 (15) 142 (14)
~
""-
191 (40) 66 (37) SR (ft-I5) 105 (17) -37(16) P NS <.10 <.02 In the SS IJ'OUp 10/14 .ubJecta Increased 68-00-' .h!It In tbt SR IJ'OUp 12/15 decreased' 8-00-' upon dietary Na- chan... Increased 6&-hydrol)'latlon of .terolcla could pl.y • role In ....bsequent BP elevation In SS Mrlcan-Amerlcaa Ido"centa. FlIt......
ltudl_1l1II determine whether Increased CYP3A ICtlvlty or concentration of .ubstrate lCCOunta for lncreMed Ul'tnar7 Illcrelloa of 68-00-' In SS .ubJec:ta, upon IOInI !'rom a low to hlp aodJwa diet.
Key Words: Salt-sensitive. Hypertension. CYP3A. 6-Beta-OH-F, African-American hypertensives
Friday, May 17, 12:00 pm
Friday, May 17, 12:15 pm
PREDICTIVE VALUE OF SODIUMILIDUUM COUNTER. TRANSPORT ON BLOOD PRESSURE CHANGES IN MIDDLE-AGED MEN: A 7·YR FOLLOW·UP STUDY ~l E Ragone l , 4F Stingal, R S Fraseatore2 E Farinaro , M Trevisan , U Candura I & P Strazzullo. l• I: of Internal Med. & Metabolic Oil., 2: Dept. of Biochemistry I: lost. of Community Medicine ·University of Naples "Federico If'. Italy; 4: lost. of Preventive Medicine, SUNY at Buffalo U.S.A.; I: Olivetti Medical Center, Naples, Italy. ' An elevated red blood cell lOdiumllithium countertransport (NaILi C1) is associated with high blood pressure and metabolic abnormalities. To evaluate the predictive power of NaILi CT with regard to changes in blood pressure (BP) over time, we examined a group of men participating in the 7·yr follow-up of the Olivetti study, a prospective investigation of coronary heart disease risk factors in Naples, Italy. One twenty si" untreated middle-aged men had NalLi CT measured both in 1987 and 1994. NalLi CT was highly stable over time (1987: 285:1:95; 1994 293:1:104 J.lIIlOI x I RBe- 1 x h· l; Pearson's correlation coefficient between the two measurements 0.80, p
INCREASED URINE ALBUMIN EXCRETION (UAE) IN SALT·SENSITIVE (SS) PATIENTS wrm HYPERTENSION (EH) R Bjgazzi. S Bianchi. and VM Campese·. Division Nephrol, Livorno, Italy. and Univ. of Southern California. Los Anieles. CA. We previously showed increased glomerular capillary preuure in SS hypertensives and suggested that this may underlie the greater propensity of these patients to develop renal failure. In this study. we have tested whether an association exists between salt-sensitivity and risk of renal disease. determined by UAE. To determine salt·sensitivity, patients were given a diet containing a low (10 mEq/day) Na+ intake for 1 week followed by a high (250 mEq/day) Na+ intake for 1 more week. Sodium sensitivity index was calculated as the ratio of the changes in mean arterial pressure (MAP) to the changes in urine Na+ from the low to the high Na+ intake. Thirty. four patients were classified as SS. and 62 as saltresistant (SR). Age (47t1.7 vs. 46t1.2 years). and body·maBS index (26±0.4 vs. 25tO.4 Kglm2 ) were ~imilar betw~en SS and SR. During high Na+ Intake. MAP mcreased by 16±O.8 nun Hg in SS and by 2.9±0.5 nun Hg in SR. UAE was higher in SS than in SR (36.2±4.2 VS. 16.3±1.9 mg/24 hr; P
Iaconc"
hm.
Kay wOrds:Hypertenaion. Salt-sensitivity,
Urine albumin excretion.
13A
ORALS: ainical Genetics
Friday, May 17, 11:30 am
Friday, May 17, 11:45 am
OBESITY GENE IS NOT LINKED WITH BODY MASS INDEX NOR ESSENTIAL HYPERTENSION IN AFRICAN AMERICAN SIBLINGS. M. Heur, M.P. Rutkowski", C. Klanke, Y.R. Su, V. Carter", M.e. Reif", A. Menon. University of Cncinnatl College of Medicine, Cncinnatl, OH. The human homologue of the obesity gene (Ob) has recently been identified (Nature 1994;372:425-432). We analyzed linkage In moderately obese, African American siblings with essential hypertension using locus 0751875, a tightly linked polymorphism (Genome Research 1995;5:5-12). We studied 147 hypertensive African Americans in 67 sibships. 98 were female, 49 male. Mean age was 50 ± 11 (sd). Mean body mass Index (BMI) was 32.3 ± 7 kg/mI. Mean systolic and diastolic pressures were 145 ± 19 and 92 ± 13 at a mean of 1.7 anti-hypertensive medications. Heterozygosity score of this polymorphic marker was 0.90. The Sibpal subroutine of S.AG.E. was used to analyze the data (U.S.P.H.S. Resource grant 1 P41 RR03655). Sibling pair linkage analysis using the log transformation of BMI as the quantitative trait showed:
EFFECT 0' DIETAIlY SODIUM (NA, ON VIlINAIlY 6-BETA. BYDROXYCORTISOL EXCRETION IN SALT-SENS111VE (SS) AND SALT-RESISTANT (SJl) ADOLESCENT AFRICANAMERICANS. 1M..IJg0. DK W1IJoII, L Kramer, CO Wetllnll!On,
Trait Locus d.f. BMI Db
66
Mean Shared Alleles full sibs half sibs 0.43 0.18
Tvalue .(J.93
Pvalue 0.18
(lnteroopt- 0.10, Slope - -.031)
Affected sibling pair linkage analysis to determine linkage with the phenotype of essential hypertension showed: Estimated Alleles Identical By Descent TPfull sibs half sibs value value • pain mean ad • pain mean ad 73 0.43 0.34 5 0.17 0.24 -1.9 1.00 In conclusion, we could not demonstrate linkage with the phenotype of moderate obesity nor essential hypertension in African American hypertensive sibling pairs. However, we cannot exclude linkage In Individuals with more severe obesity. Key Words:
Obesity, Genetics, Essential Hypertension, Human, AfrIcan Americans
Modical Collea' of VIrIlIl1.. RIchmond, VJraInJa. Cor\llOl 00 II tbt aubsll'ate for family 3A cytochrome P~ enzyme (CYP3A) conYenloa to 6&-hydrol)'eortllol (68-00-1). Urtnary 68-00·F/l'n. , nUo II a propc»ed Indell of In mo CYP3A IlCtIvlty. PnllmlnU'1 lIudl_ haw au..-ted tbt pNence of an tncn.ed nlIo In ••ubset of Mrlcan-Amertcan _tlal hyperteDllwa. Con'eIatIona bdween l'IIIaI CYP3A IClMty and bloocl Pl'llaun (BP) with \'II'18tIoa In .....1raIn IIIId drvl treatment In tbt spontaneous Iy hypen-Ive nt .... aIao consillentwltb • role of CYP3A In tbt pal!lopella of BP elevation In thll .netlc modeL W. ha.......uated tbt urlnU'1 elCl'etIon of 68-00-' In a
prevlo...ly charac:tertzed aubset of ICIoIeacent normotensl.. MrlcanAmerkanI determined to be SS or SR. A~ta __ d.sItled • SS If their mean BP Increued >5 mm 01 !'rom • 5 day low N.+ diet (50 mEqJ24hr) to • 10 day hlp Na+ diet (NaCl .upp'-at -150 mEqJ24hr). 68-00-' _ m_ured by ny absorbance oa _ .... ph_ BPLC with pre-atractloa or lII'Int oa two CII1rtdl_ (reYene IIIId normal ph-. sequentially) and II reported • IlCIfU 1m.
Pkl
SS (n-l4)
Iel!!: 115 (15) 142 (14)
~
""-
191 (40) 66 (37) SR (ft-I5) 105 (17) -37(16) P NS <.10 <.02 In the SS IJ'OUp 10/14 .ubJecta Increased 68-00-' .h!It In tbt SR IJ'OUp 12/15 decreased' 8-00-' upon dietary Na- chan... Increased 6&-hydrol)'latlon of .terolcla could pl.y • role In ....bsequent BP elevation In SS Mrlcan-Amerlcaa Ido"centa. FlIt......
ltudl_1l1II determine whether Increased CYP3A ICtlvlty or concentration of .ubstrate lCCOunta for lncreMed Ul'tnar7 Illcrelloa of 68-00-' In SS .ubJec:ta, upon IOInI !'rom a low to hlp aodJwa diet.
Key Words: Salt-sensitive. Hypertension. CYP3A. 6-Beta-OH-F, African-American hypertensives
Friday, May 17, 12:00 pm
Friday, May 17, 12:15 pm
PREDICTIVE VALUE OF SODIUMILIDUUM COUNTER. TRANSPORT ON BLOOD PRESSURE CHANGES IN MIDDLE-AGED MEN: A 7·YR FOLLOW·UP STUDY ~l E Ragone l , 4F Stingal, R S Fraseatore2 E Farinaro , M Trevisan , U Candura I & P Strazzullo. l• I: of Internal Med. & Metabolic Oil., 2: Dept. of Biochemistry I: lost. of Community Medicine ·University of Naples "Federico If'. Italy; 4: lost. of Preventive Medicine, SUNY at Buffalo U.S.A.; I: Olivetti Medical Center, Naples, Italy. ' An elevated red blood cell lOdiumllithium countertransport (NaILi C1) is associated with high blood pressure and metabolic abnormalities. To evaluate the predictive power of NaILi CT with regard to changes in blood pressure (BP) over time, we examined a group of men participating in the 7·yr follow-up of the Olivetti study, a prospective investigation of coronary heart disease risk factors in Naples, Italy. One twenty si" untreated middle-aged men had NalLi CT measured both in 1987 and 1994. NalLi CT was highly stable over time (1987: 285:1:95; 1994 293:1:104 J.lIIlOI x I RBe- 1 x h· l; Pearson's correlation coefficient between the two measurements 0.80, p
INCREASED URINE ALBUMIN EXCRETION (UAE) IN SALT·SENSITIVE (SS) PATIENTS wrm HYPERTENSION (EH) R Bjgazzi. S Bianchi. and VM Campese·. Division Nephrol, Livorno, Italy. and Univ. of Southern California. Los Anieles. CA. We previously showed increased glomerular capillary preuure in SS hypertensives and suggested that this may underlie the greater propensity of these patients to develop renal failure. In this study. we have tested whether an association exists between salt-sensitivity and risk of renal disease. determined by UAE. To determine salt·sensitivity, patients were given a diet containing a low (10 mEq/day) Na+ intake for 1 week followed by a high (250 mEq/day) Na+ intake for 1 more week. Sodium sensitivity index was calculated as the ratio of the changes in mean arterial pressure (MAP) to the changes in urine Na+ from the low to the high Na+ intake. Thirty. four patients were classified as SS. and 62 as saltresistant (SR). Age (47t1.7 vs. 46t1.2 years). and body·maBS index (26±0.4 vs. 25tO.4 Kglm2 ) were ~imilar betw~en SS and SR. During high Na+ Intake. MAP mcreased by 16±O.8 nun Hg in SS and by 2.9±0.5 nun Hg in SR. UAE was higher in SS than in SR (36.2±4.2 VS. 16.3±1.9 mg/24 hr; P
Iaconc"
hm.
Kay wOrds:Hypertenaion. Salt-sensitivity,
Urine albumin excretion.
13A