Effects of Angiotensin II on the Growth of Vascular Smooth Muscle Cells

BACKGROUND AND OBJECTIVES: The octapeptide hormone of the renin-angiotensin system, angiotensin ii, regulates a wide variety of physiological responses including salt and water balance, blood pressure, and vascular tone. Contradictory results have been reported regarding the effects of angiotensin ii on vascular smooth mu-scle cell (VSMC) proliferation. The aim of the present study was to investigate the direct effect of angiotensin ii on the growth of VSMC. MATERIALS AND METHOD: Rat aortic smooth muscle cells were obtained by the combined collagenase and elastase methods. Cells between the 4th and 8th passages were used for the experiments. Cultures were treated daily for 3 days with either angiotensin ii alone or angiotensin ii with equimolar concentrations of saralasin. Incorporated radioactivity of [3H]thymidine and [14C]phenylalanine was measured by liquid scintillation spectrometry. RESULTS: Angiotensin ii increased [14C]phenyalanine incor-poration about 20-30%, and saralasin completely blocked the stimulation by angiotensin ii. However, there was no significant increase in [3H]thymidine incorporation by angiotensin ii stimulation in this study. CONCLUSION: These results suggest that angiotensin ii alone induces cellular hypertrophy but has no detectable mitogenic activity in cultured rat aortic VSMC.

Correlation of Complex Ventricular Arrhythmias with Left Ventricular Hypertrophy and Their Prognostic Significances / 대한내과학회지

OBJECTIVES: Echocardiographically determined left ventricular hypertrophy is associated with increased risk for sudden cardiae death and for complex ventricular arrhythmias in 24-hour ambulatory electrocardiographic monitoring. In subjects with left ventricular hypertrophy, the presence of asymptomatic complex ventricular arrhythmias is associated with higher incidence of sudden cardiac death and higher cardiovascular mortality. However, their accurate relationship and prognostic significances have been remained to be established. The purpose of this study was to evaluate the relationship between complex ventricular arrhythmias, left ventricular hypertrophy, and sudden cardiac death in Korean patients. METHODS: Twenty four hour ambulatory electrocardiographic monitoring, echocardiographic data and medical records were reviewed in 360 subjects from 1991 to 1994. We evaluated the relationship between complex ventricular arrhythmias and left ventricular mass index, and the prognostic values of them. Of the 360 subjects, 187 could be followed up for one to four years. The mean follow-up period was 2.8 years. RESULTS: The incidence of complex ventricular arrhythmias was significantly correlated with left ventricular mass index and ejection fraction in all subjects. During the follow-up periods, seven of 187 subjects died from sudden cardiac death. Six of them had complex ventricular arrhythmias with left ventricular hypertrophy. CONCLUSION: The incidence of complex ventricular arrhythmias was significantly correlated with echocardiographically determined left ventricular hypertrophy and it is suggested that subjects with complex ventricular arrhythmias combined with left ventricular hypertrophy have higher risk for sudden cardiac death.

The Effect of Enalapril on the Peak Rates of Left Ventricular Wall Movement in Patients with Dilated Cardiomyopathy / 대한내과학회지

OBJECTIVE: Angiotensin-converting enzyme inhibitors have been shown to improve survival in patients with congestive heart failure. To evaluate the efficacy of enalapril in patients with dilated cardiomyopathy during concurrent treatment with digoxin and diuretics, the peak rates of left ventricular movement were assessed after 6 months of follow-up by digitized echocardiography. METHODS: Using a high quality digitizer, continuous measurement of left ventricular dimension and its rate of change (dD/dt) were obtained throughout the cardiac cycle. Normalized rates of wall movement (dD/dt/D) were used for comparison. RESULTS: 1) Compared with control subjects, patients with dilated cardiomyopathy showed much lower Peak(-) dD/dt and Peak(-) dD/dt/D. 2) Peak(+) dD/dt and Peak(+) dD/dt/D were also depressed in patients. 3) Peak dD/dt improved significantly (p<0.05) in the enalapril group (n=16), but did not change in the conventional treatment group (n=20) after 6 months. Peak dD/dt/D improved approximately (p<0.005) in the enalapril group. 5) There were no deaths in 2 treatment groups during initial 6 months, but 3 patients in the conventional treatment group died suddenly during 1 year of follow-up. CONCLUSION: The present study has shown that left ventrieular Peak dD/dt and Peak dD/dt/D are significantly depressed in patients with dilated cardiomyopathy. Enalapril appears to provide well-tolerated and effective long-term therapy by improving peak rates of left ventricular movement in patients with dilated cardiomyopathy.

Effect of Hormone Replacemcet Therapy on Lipoprotein(a) and Lipids in Postmenopausal Women: Influence of Duration of Medication / 대한내과학회지

OBJECTIVES: Hormone replacement therapy(HRT) in postmenopausal women decreases lipoprotein(a) [Lp(a)]. The influences of progesterone on Lp(a) and lipids, administered with estrogen, are controversial. However, previous studies had variable duration of therapy, and there was no report evaluating the effect of the duration of medication. METHODS: A total 246 postmenopausal women were divided into 4 groups: group A; 0.625mg conjugated equine estrogen(CEE)(n=90), group B; 0.625mg CEE plus 5mg medroxyprogesterone acetate(MPA)(n=35), group C; 0.625mg CEE plus 10mg MPA(n=43), and group D; 2mg estradiol valerate(E2) plus 0.5mg norgestrel(N)(n=76). Lp(a) and lipids levels were measured before, 2, 6 and 12 months after HRT. RESULTS: In total subjects, Lp(a) was decreased with medication for 2 months by 20.7%(p<0,0001). Compared with levels at 2 months after medication, levels at 6 and 12 months revealed further reduction(p<0.001) by 5.3% and 9.0% respectively. Medication for 2 months increased HDL-C in group A, not changed in group B and C, and decreased in group D. After 12 months, HDL-C levels were increased in Group A, B, and C, and not changed in group D, In total subjects, low density lipoprotein-cholesterol(LDL-C) was decreased by 12.2% after 2 months(p<0.001). Compared with levels at 2 months after medication, LDL-C level was decreased by 3.4% after 6 months(p<0.001) and there was no further reduction after 12 months. CONCLUSION: The effect of hormone replacement therapy on Lp(a) and lipids were dependent upon the duration of medication. Inconsistent results in previous studies can be partially explained by the difference in this parameter.

Ultrastructural Changes of the Aorta in Spontaneously Hypertensive Rats and the Effect of High Cholesterol Diet

BACKGROUND: Vascular lesions are the major cause of morbidity and mortality in hypertensive patients. However, the pathologic characteristics of gradually evolving, chronic hypertension have not been adequately studied and the mechanism by which hypertension accelerates atherosclerosis is still uncertain. This study was undertaken to invertigate the ultrastructural changes of the aorta and the effect of high cholesterol diet in spontaneously hypertensive rats(SHR). METHODS: Spontaneously hypertensive rats (n=80, male, 5 weeks old) and Wistar rats (n=40, male, 5 week old) were used. Forty SHR were fed with 2% cholestrol diete, while the remainder with control diet. Systolic blood pressure was measured weekly until 16 weeks after birth, and then biweekly until 40 weeks after birth. Transmission and scanning electron microscopy were used to evaluate ultrastrucural changes of the aorta. RESULTS: 1) The blood pressure of SHR rose stedily and progressively from the 5 weeks after birth and reached nearly 190mmHG at the 16 weeks after birth. 2) In SHR, the subendothelial component contained finely granular substances, abundant fibrillar collagen and elastin. Infiltration of the mononuclear blood leukocytes into the intima was frequently seen. 3) Endothelium from cholestrol-fed SHR did exhibit numerous pinocytotic vesicles and contained many cytoplasmic filaments. There were a number of large mononuclear lipid-filled cells in the intimal lesions. Blistering of the endothelial plasma membrane was also observed in high cholesterol diet-fed SHR. Later on, adhesion of platelets, febrin, and white blood cells as well as damage of intima shown as multiple small holes were more marked. 4) There was no significant difference in systoloic blood pressure between high cholesterol diet-fed and control diet-fed SHR. CONCLUSION: In the aorta of SHR, the most prominent change was an expansion of the subendothelial space and infiltration of the mononuclear leukocytes into the intima. The present study showed that the SHR was indeed a reliable model for the essential hypertension. In some SHR, high cholesterol diet could induce more pronounced vascular lesions, which were enhanced by hypertension.