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Dopaminergic control of aldosterone release is not determined by race or salt sensitivity
AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
expression in SHR (173 ⫾ 12%) and had a small stimulatory effect in WKY (119 ⫾ 6%). These actions were inhibited by PD98059, but not by SB202190. Ang II dose-dependently increased 3H-thymidine and 3H-leucine incorporation. Responses were enhanced (p ⬍ 0.02) in SHR. Pretreatment of cells with PD98059 attenuated Ang II-induced growth effects and normalized responses in SHR. SB212190 did not alter DNA synthesis, but significantly reduced (P ⬍ 0.05) protein synthesis in SHR (232 ⫾ 12 vs 132 ⫾ 117%). Ang II-stimulated effects were inhibited by irbesartan, AT1 receptor antagonist, but not by PD123319, AT2 receptor blocker. Thus Ang II-mediated activation of vascular ERK1/2 and p38 is increased in SHR. Augmented c-fos and growth responses are generated primarily via ERK1/2. p38 influences Ang II-induced hypertrophy in SHR but not in WKY. These results indicate differential roles of ERK1/2 and p38 in AT1-stimulated VSMC growth, which may contribute to vascular remodeling in genetic hypertension. (Supported by Bristol-Myers Squibb/Sanofi) Key Words: Signal transduction; angiotensin II; vascular smooth muscle growth; extracellular signal-activated kinase
I013 THE INFLUENCE OF ESSENTIAL HYPERTENSION ON THE PECULIARITIES OF ISCHEMIC HEART DISEASE CORSE COMPLICATED WITH HEART FAILURE 1ST AND 2ND STAGES I.V. Melnytskyy*, V.K. Tashchuk, R.B. Chaplinski, O.S. Polyanskaya. Bucovinian Medical Academy and Cardiocenter, Chernivtsi, Ukraine With the purpose of assessing the influence of Essential Hypertension (EH) upon the course of ischemic heart disease (IHD) complicated with Heart Failure (HF) 1ST and 2ND stages (1st and 2nd groups) 128 patients with standing myocardial infarction (MI) within 1.5–2 months from its beginning were examined. Captopril (BMS) was administered as antihypertensive medication (25 mg daily). Transesophageal electrocardiostimulation (TEES), echocardiography (EchoCG) as well as Holter Monitoring of ECG (HM ECG) were applied. In the 2nd group of the patients in comparison with the 1st group there was defined a reduction of ejection fraction (EF) as per the results of EchoCG (40,5 ⫾ 0,6 and 49,5 ⫾ 1,4%, p ⬍ 0,001) and TEES data (123,7 ⫾ 0,8 and 145,7 ⫾ 2,5 imp/min, p ⬍ 0,001). The results of HM ECG have shown that episodes of painful myocardial ischemia were absent in the 1st group while in the 2nd group they have been registered in 57,0 ⫾ 4,1% patients. The episodes of silent myocardial ischemia were 26,0 ⫾ 3,6 and 25,0 ⫾ 0,7%, respectively (p ⬍ 0,5). The administration of Captopril (BMS) has been resulted in increase the frequency of the cessation TEES in the 1st and the 2nd group of the patients (7,3% and 5,4%, p ⬍ 0,001). Thus the results of TEES prove the existence of an essential influence of EH on the limitation of coronary reserve in patients with MI complicated with HF 1ST and 2ND stages. The administration of Captopril (BMS) has been resulted in the essential increase of coronary reserve.
POSTERS: Renin-Angiotensin-Aldosterone
179A
Key Words: Standing myocardial infarction; Holter monitoring; coronary reserve; heart failure I014 DOPAMINERGIC CONTROL OF ALDOSTERONE RELEASE IS NOT DETERMINED BY RACE OR SALT SENSITIVITY E.B.D. Ripley*, D.A. Sica* Medical College of Virginia at Virginia Commonwealth University, Richmond, VA Dopamine exerts a tonic inhibitory effect on aldosterone (ALDO) release. This inhibitory effect can be blocked by administration of metoclopramide. In order to evaluate the effect of race and salt sensitivity on the dopaminergic control of ALDO release, hypertensive patients determined to be either salt sensitive (SS) or salt resistant (SR) were given IV metoclopramide followed by serial plasma ALDO levels. 12 black and 9 white hypertensive patients off all medication for 2 weeks received 10 mg of IV metoclopramide with serial ALDO levels at 0, 15, 30, and 60 minutes. The following week SS was determined by change in blood pressure post 2L of NS compared to post one day of furosemide 40 mg PO TID. Patients with an decrease in mean arterial pressure of ⱖ10 mm Hg were deemed SS. Data is presented as mean ⫾ SD, T tests were performed with Bonferroni correction where appropriate.
Black White Salt Sensitive Salt Resistant
Male/Female
Age (yrs)
Weight (Kg)
4/8 3/6 2/8 5/6
44 ⫾ 00 46 ⫾ 00 52 ⫾ 7 38 ⫾ 7*
99 ⫾ 23 93 ⫾ 19 87 ⫾ 21 105 ⫾ 17*
*p ⬍ 0.05 compared to salt sensitive Plasma Aldosterone (ng/dl)
Black White Salt Sensitive Salt Resistant
0 min
15 min
30 min
60 min
9⫾5 9⫾4 10 ⫾ 5 7⫾4
21 ⫾ 14 20 ⫾ 6 22 ⫾ 12 19 ⫾ 9
22 ⫾ 13 22 ⫾ 6 25 ⫾ 11 19 ⫾ 9
20 ⫾ 11 21 ⫾ 7 22 ⫾ 9 19 ⫾ 10
Primary matching for race, age and weight lessened the confounding effect of these variables. Consistent with previous epidemiological studies, SS patients were older and SS females were more commonly post or peri-menopausal. Race, gender, or salt-sensitivity status did not influence dopamine-related ALDO release. Key Words: Race; salt sensitivity; aldosterone I015 SALT-SENSITIVE HYPERTENSION CAUSED BY LONG-TERM CAPTOPRIL TREATMENT IN SPRAGUE-DAWLEY RATS M.S. Muntzel*, B. Waugh, and A. Akinsefunmi. Department of Biological Sciences, Lehman College, Bronx, NY, and Department of Biology, Hostos Community. College, Bronx, NY
expression in SHR (173 ⫾ 12%) and had a small stimulatory effect in WKY (119 ⫾ 6%). These actions were inhibited by PD98059, but not by SB202190. Ang II dose-dependently increased 3H-thymidine and 3H-leucine incorporation. Responses were enhanced (p ⬍ 0.02) in SHR. Pretreatment of cells with PD98059 attenuated Ang II-induced growth effects and normalized responses in SHR. SB212190 did not alter DNA synthesis, but significantly reduced (P ⬍ 0.05) protein synthesis in SHR (232 ⫾ 12 vs 132 ⫾ 117%). Ang II-stimulated effects were inhibited by irbesartan, AT1 receptor antagonist, but not by PD123319, AT2 receptor blocker. Thus Ang II-mediated activation of vascular ERK1/2 and p38 is increased in SHR. Augmented c-fos and growth responses are generated primarily via ERK1/2. p38 influences Ang II-induced hypertrophy in SHR but not in WKY. These results indicate differential roles of ERK1/2 and p38 in AT1-stimulated VSMC growth, which may contribute to vascular remodeling in genetic hypertension. (Supported by Bristol-Myers Squibb/Sanofi) Key Words: Signal transduction; angiotensin II; vascular smooth muscle growth; extracellular signal-activated kinase
I013 THE INFLUENCE OF ESSENTIAL HYPERTENSION ON THE PECULIARITIES OF ISCHEMIC HEART DISEASE CORSE COMPLICATED WITH HEART FAILURE 1ST AND 2ND STAGES I.V. Melnytskyy*, V.K. Tashchuk, R.B. Chaplinski, O.S. Polyanskaya. Bucovinian Medical Academy and Cardiocenter, Chernivtsi, Ukraine With the purpose of assessing the influence of Essential Hypertension (EH) upon the course of ischemic heart disease (IHD) complicated with Heart Failure (HF) 1ST and 2ND stages (1st and 2nd groups) 128 patients with standing myocardial infarction (MI) within 1.5–2 months from its beginning were examined. Captopril (BMS) was administered as antihypertensive medication (25 mg daily). Transesophageal electrocardiostimulation (TEES), echocardiography (EchoCG) as well as Holter Monitoring of ECG (HM ECG) were applied. In the 2nd group of the patients in comparison with the 1st group there was defined a reduction of ejection fraction (EF) as per the results of EchoCG (40,5 ⫾ 0,6 and 49,5 ⫾ 1,4%, p ⬍ 0,001) and TEES data (123,7 ⫾ 0,8 and 145,7 ⫾ 2,5 imp/min, p ⬍ 0,001). The results of HM ECG have shown that episodes of painful myocardial ischemia were absent in the 1st group while in the 2nd group they have been registered in 57,0 ⫾ 4,1% patients. The episodes of silent myocardial ischemia were 26,0 ⫾ 3,6 and 25,0 ⫾ 0,7%, respectively (p ⬍ 0,5). The administration of Captopril (BMS) has been resulted in increase the frequency of the cessation TEES in the 1st and the 2nd group of the patients (7,3% and 5,4%, p ⬍ 0,001). Thus the results of TEES prove the existence of an essential influence of EH on the limitation of coronary reserve in patients with MI complicated with HF 1ST and 2ND stages. The administration of Captopril (BMS) has been resulted in the essential increase of coronary reserve.
POSTERS: Renin-Angiotensin-Aldosterone
179A
Key Words: Standing myocardial infarction; Holter monitoring; coronary reserve; heart failure I014 DOPAMINERGIC CONTROL OF ALDOSTERONE RELEASE IS NOT DETERMINED BY RACE OR SALT SENSITIVITY E.B.D. Ripley*, D.A. Sica* Medical College of Virginia at Virginia Commonwealth University, Richmond, VA Dopamine exerts a tonic inhibitory effect on aldosterone (ALDO) release. This inhibitory effect can be blocked by administration of metoclopramide. In order to evaluate the effect of race and salt sensitivity on the dopaminergic control of ALDO release, hypertensive patients determined to be either salt sensitive (SS) or salt resistant (SR) were given IV metoclopramide followed by serial plasma ALDO levels. 12 black and 9 white hypertensive patients off all medication for 2 weeks received 10 mg of IV metoclopramide with serial ALDO levels at 0, 15, 30, and 60 minutes. The following week SS was determined by change in blood pressure post 2L of NS compared to post one day of furosemide 40 mg PO TID. Patients with an decrease in mean arterial pressure of ⱖ10 mm Hg were deemed SS. Data is presented as mean ⫾ SD, T tests were performed with Bonferroni correction where appropriate.
Black White Salt Sensitive Salt Resistant
Male/Female
Age (yrs)
Weight (Kg)
4/8 3/6 2/8 5/6
44 ⫾ 00 46 ⫾ 00 52 ⫾ 7 38 ⫾ 7*
99 ⫾ 23 93 ⫾ 19 87 ⫾ 21 105 ⫾ 17*
*p ⬍ 0.05 compared to salt sensitive Plasma Aldosterone (ng/dl)
Black White Salt Sensitive Salt Resistant
0 min
15 min
30 min
60 min
9⫾5 9⫾4 10 ⫾ 5 7⫾4
21 ⫾ 14 20 ⫾ 6 22 ⫾ 12 19 ⫾ 9
22 ⫾ 13 22 ⫾ 6 25 ⫾ 11 19 ⫾ 9
20 ⫾ 11 21 ⫾ 7 22 ⫾ 9 19 ⫾ 10
Primary matching for race, age and weight lessened the confounding effect of these variables. Consistent with previous epidemiological studies, SS patients were older and SS females were more commonly post or peri-menopausal. Race, gender, or salt-sensitivity status did not influence dopamine-related ALDO release. Key Words: Race; salt sensitivity; aldosterone I015 SALT-SENSITIVE HYPERTENSION CAUSED BY LONG-TERM CAPTOPRIL TREATMENT IN SPRAGUE-DAWLEY RATS M.S. Muntzel*, B. Waugh, and A. Akinsefunmi. Department of Biological Sciences, Lehman College, Bronx, NY, and Department of Biology, Hostos Community. College, Bronx, NY