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Biomedical subjects

Y A Ding

Publications and source records attributed to Y A Ding.

At least 109 records · Page 6Linked to original sources

Antihypertensive and metabolic effects of tiapamil.

Tiapamil, a new calcium antagonist, was evaluated for its antihypertensive and metabolic effects in a long-term (58 weeks) drug trial in 20 adult outpatient mild to moderately hypertensive subjects. Baseline systolic and diastolic blood pressure dropped after initiation of treatment and was significantly reduced after 4 weeks of treatment, further improving until the termination of the study. There was no impairment of renal and hepatic functions. Electrolytes, plasma aldosterone, plasma renin activity, as well as plasma lipids were not significantly altered during the course of therapy. Fasting blood sugar determinations and oral glucose tolerance test showed significant reductions from the baseline level as a result of the drug treatment. In conclusion, tiapamil is a metabolically safe and effective antihypertensive drug for long-term use.

Adult↗

Detection of dysfunctioning mitral prosthetic regurgitation: transesophageal echocardiography in comparison with transthoracic echocardiography and angiography.

Transesophageal echocardiography has been increasingly used in addition to the transthoracic approach. It not only allows an unobstructed window for viewing the left atrium, but also provides high-quality imaging to improve diagnosis of prosthetic valve dysfunction. To determine the value of transesophageal echocardiography in detection of dysfunctioning mitral prosthetic regurgitation, 11 patients clinically suspected of dysfunctioning mitral prosthesis were studies by transthoracic, transesophageal echocardiography and was documented by a left ventricular angiography. There were 7 biological tissue valves and 4 metallic Bjork-Shiley valves. Compared with a left ventricular angiography, the transthoracic approach to 8 patients made an underestimation of the grade of regurgitation. The angiographic grading confirmed the transesophageal approach in all patients except one who was graded as mild regurgitation by left ventricular angiography, moderate regurgitation by transesophageal echocardiography, but no regurgitation by transthoracic echocardiography. Our results indicated that in patients with suspected mitral prosthetic dysfunction, a transesophageal echocardiography is more sensitive than a transthoracic echocardiography in detecting mitral regurgitation.

Adult↗

Progression of cardiac hypertrophy during long term calcium antagonist treatment with tiapamil.

Hypertension complicated by left ventricular hypertrophy is associated with increased morbidity as it leads to left ventricular systolic and diastolic dysfunction. Thus, in the treatment of hypertension, a desirable goal is the regression of left ventricular hypertrophy. Tiapamil, a new calcium antagonist, was evaluated in a 58 week open study to determine its effect on left ventricular mass in relation to its ability to lower blood pressure. Twenty adult patients with mild to moderate hypertension were entered into the study. Blood pressure was significantly reduced from 166 +/- 16/105 +/- 7 mmHg before treatment to 142 +/- 9/88 +/- 4 mmHg after 58 weeks. The posterior and interventricular septal wall thickness and left ventricular systolic dimension did not show any significant change by the end of the trial. On the other hand, left ventricular diastolic dimension, ejection fraction, and left ventricular mass increased significantly (P less than 0.05). Other laboratory parameters were not affected during treatment with the exception of a moderate decrease in the blood glucose. Side effects were mild and self-limiting, and no patients were withdrawn from the study. Although tiapamil appears to be an effective and well-tolerated drug in mild to moderate hypertension, it failed to reduce left ventricular mass.

Administration, Oral↗

Effects of dietary polyunsaturated fatty acid on platelet aggregation in rats.

In the present study, we changed the fatty acid profile in blood and platelet membranes by dietary manipulation, and examined the effect on platelet aggregation in rats. Fifty-five rats were divided into five groups and fed for 56 days with 1% cholesterol and different types of fatty acid-rich diets: basal, lard, lard + fish oil, soybean oil, and soybean oil + fish oil. a decrease in serum arachidonic acid (20:4, omega-6, AA) and an increase in serum eicosapentaenoic acid (20:5, omega-3, EPA) were found in all experimental dietary groups fed with refined fish oil. Similar changes in the polyunsaturated fatty acids were also found in the platelet membrane phospholipids. Platelet aggregation, quantitated by the slope and height of the aggregation curve induced by different concentrations of ADP in a platelet aggregometer, was inhibited in all groups fed with refined fish oil. This inhibition of platelet aggregation may be related to an increase in the ratio of EPA and AA in the platelet membrane phospholipids after dietary manipulation. The differences in the platelet aggregation and thromboxane B2 (TXB2) concentration between the lard and the lard + fish oil groups were more profound than that between the soybean oil and the soybean oil + fish oil group. However, the malondialdehyde (MDA) concentration revealed no significant differences between the five groups.

Animals↗

Effects of exercise and ticlopidine on platelet function and prostanoids in patients with old myocardial infarction.

Twenty-eight subjects, 16 with old myocardial infarction (OMI) and a control group of 12, received ticlopidine 250 mg/day for 4 weeks. All subjects underwent the standard Bruce protocol exercise test before and after therapy. Blood was collected from a peripheral vein to study platelet function at pre-exercise (rest), peak exercise (end point), and 6 min post-exercise (recovery). Platelet count, platelet aggregatory response, plasma thromboxane B2 (TXB2), and 6-keto-PGF 1 alpha were measured by Coulter counter, aggregometry, and radioimmunoassay, respectively. The platelet count, aggregatory response (induced by ADP, adrenalin, and collagen) and the plasma concentration of TXB2 and 6-keto-PGF 1 alpha were not significantly affected by exercise in the OMI and control groups. Overall, there were no significant changes in exercise duration, heart rate, and blood pressure in both groups before or after ticlopidine treatment, with some minor exceptions. There were no significant changes in the peripheral blood profiles, the bleeding and coagulation times, the blood chemistry data, and the platelet counts between the groups before or after treatment. There was a significant decrease in collagen- and ADP-induced platelet aggregation in both groups after ticlopidine therapy. Prior to treatment, a higher plasma TXB2 concentration was noted in the OMI group during and after exercise; the difference was no longer statistically significant after ticlopidine therapy when both groups were compared. There was a significant reduction in the TXB2 levels in the OMI group after ticlopidine treatment despite exercise. Before therapy, plasma 6-keto-PGF 1 alpha was significantly elevated in the OMI group before or after exercise but was not statistically significant after ticlopidine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Antihypertensive and renal effects of cilazapril and their reversal by angiotensin in renovascular hypertensive rats.

1. The antihypertensive and renal effects of cilazapril, a new angiotensin converting enzyme inhibitor, were evaluated in both two-kidney, one-clip Goldblatt hypertensive rats (n = 11) and normotensive rats (n = 6). 2. Intravenous infusion of cilazapril (1 mg/kg followed by 25 micrograms min-1 kg-1) caused significant reductions of blood pressure from 163 +/- 3 to 122 +/- 4 mmHg and from 157 +/- 2 to 113 +/- 3 mmHg in two separate groups of hypertensive rats and from 124 +/- 1 to 105 +/- 2 mmHg in normotensive rats. The hypotensive effect in terms of absolute value of percentage change was greater in hypertensive rats than in normotensive rats (41 +/- 6 vs 20 +/- 3 mmHg or 25 +/- 4% vs 16 +/- 2%, respectively). 3. Cilazapril increased glomerular filtration rate, urine flow, and absolute and fractional excretion rates of sodium and potassium in the non-clipped kidney of hypertensive rats. In contrast, the clipped kidney exhibited a depressed renal function during cilazapril infusion. 4. In normotensive rats, the hypotensive and enhanced renal function responses to cilazapril were much less than those of the non-clipped kidney of hypertensive rats. 5. Superimposed administration of either angiotensin II or angiotensin III during cilazapril infusion completely reversed the blood pressure and bilateral renal responses of cilazapril in both hypertensive and normotensive rats. 6. These results indicate that cilazapril reduces arterial pressure and enhances renal excretion mainly via inhibition of angiotensin II and angiotensin III formation.

Angiotensin II↗

Long-term effect of tiapamil in essential hypertension.

To evaluate the long-term effect of tiapamil, a new calcium antagonist, in hypertension, 20 adult patients suffering from mild to moderate hypertension were entered into a 58-week open study. In 10 patients, blood pressure returned to normal within 1-6 weeks with a daily dose of 600-900 mg tiapamil. In the remaining 10 patients, the blood pressure became normal after 8-28 weeks with a daily dose of 900-1,200 mg tiapamil. The more severe the hypertension, the higher the dose needed and the longer the time required for the blood pressure to return to normal. The overall results at the end of the 58-week treatment showed a significant decrease of the blood pressure to 142 (+/- 9)/88 (+/- 4) mmHg from a before treatment average of 166 (+/- 16)/105 (+/- 7) (p less than 0.001). There was no marked difference in the blood pressure between supine and sitting positions before or after treatment. Side effects were mild and self-limiting, with no patient being dropped from the study. Electrocardiogram (ECG) and laboratory values were not affected during the treatment with the exception of a moderate decrease in the blood glucose. Neither plasma renin activity, nor aldosterone concentration, nor serum cholesterol or triglyceride levels were altered during tiapamil administration. Tiapamil appears to be an effective and well-tolerated drug for use in mild to moderately severe hypertension.

Adult↗

Diagnostic value of maximal treadmill exercise electrocardiogram in predicting coronary artery disease for asymptomatic Chinese male subjects.

The value of maximal treadmill exercise electrocardiogram (TEE) in predicting coronary artery disease was evaluated in a consecutive series of 168 asymptomatic Chinese males, aged 41 to 57 years (mean 53) during annual physical examinations. Their resting electrocardiograms (ECGs) showed no abnormal Q-waves. The end-point of TEE achieved the age-predicted maximal heart rate, and no subjects had classic angina pectoris during or after TEE. Thirty-five subjects had positive electrocardiographic changes defined as reversible horizontal or downsloping ST-segment depression greater than or equal to 1.0 mv which lasted greater than or equal to 0.08 sec. Exercise thallium-201 (T1-201) myocardial imaging was performed on all 35 subjects with positive TEE; 30 subjects (86%) demonstrated normal and 5 abnormal scintigrams. Sixteen of the 30 cases with normal T1-201 scans underwent coronary arteriography, of which 14 showed normal arteriograms and two showed a less than 49% stenosis of the luminal diameter in one major artery. Of the 5 cases with abnormal scintigrams, 4 were found to have greater than 50% stenoses in at least one major artery, and only one case had a less than 49% stenosis of the right coronary artery. We concluded that TEE alone for asymptomatic individuals provided limited value in diagnosing significant coronary artery disease, especially in areas of low prevalence.

Adult↗

Reduced number of angiotensin II receptors on platelets in insulin-dependent diabetes.

Angiotensin II receptors on platelets were studied in 13 patients with uncomplicated type I diabetes mellitus and in 15 age-matched normal subjects. Receptor density on cells from the diabetic patients was 15% lower than the normal subjects (5.2 +/- 0.8 SD sites/platelet in diabetic patients and 6.4 +/- 0.8 in normals, P less than 0.001), but there were no differences in receptor affinity as measured by Kd (4.9 +/- 1.5 X 10(-10) mol/l in diabetic patients and 5.4 +/- 1.4 X 10(-10) mol/l in normals). Plasma concentrations of renin and angiotensin II were similar in both groups. The reduced density of angiotensin II receptors on platelets from patients with insulin-dependent diabetes may reflect a generalized abnormality of angiotensin II receptor regulation.

Adult↗

Potentiation of adrenaline-induced platelet aggregation by angiotensin II.

The effects of angiotensin II (ANG II) alone and in combination with other agonists on human platelet aggregation, thromboxane B2 (TxB2) and cytosolic [Ca2+]i were investigated. ANG II (10(-11) - 10(-7) M) alone had no direct effect on aggregation, TxB2 production or [Ca2+]i after short- (less than 2 min) or long-term (30 min) incubation. In contrast, low concentrations of ANG II (10(-11) M) enhanced adrenaline-induced platelet aggregation but high concentrations (10(-7) M) had an inhibitory effect. Moreover, ANG II (10(-11) - 10(-7) M) augmented platelet responses to the TxA2 mimetic, U44069. Pretreatment of platelets with flurbiprofen abolished this facilitatory effect of ANG II on adrenaline- but not on U44069-induced platelet aggregation. These results suggest that ANG II stimulation of agonist-induced platelet activation may be due to potentiation of the effects rather than the synthesis of TxA2.

Angiotensin II↗

Regulation of platelet receptors for angiotensin II in man.

The effects of changes in dietary intake of sodium and potassium on 125I-angiotensin II binding to platelets were studied in normal subjects. We also defined binding to platelets from patients with essential hypertension and subjects with normal blood pressure. Restriction of sodium intake in normal subjects resulted in a decrease in the number of receptor sites from 6.2 +/- 0.3 sites/cell to 4.1 +/- 0.4 sites/cell (P less than 0.01) but there were no changes in affinity as measured by the Kd. Over a range of sodium intakes from 15 to 200 mmol/day there was a negative correlation between plasma concentration of angiotensin II and receptor site concentration (rs = 0.57, P less than 0.01). Changes in dietary potassium did not affect angiotensin II binding. Angiotensin II binding was also measured in 10 patients with essential hypertension (mean blood pressure [BP] 178/107 mmHg, plasma concentrations of renin [PRC] 12 +/- 2 microU/ml and angiotensin [pANG] II 14 +/- 2 pg/ml) and 10 subjects with normal blood pressure (mean BP 112/74 mmHg, PRC 13 +/- 2 microU/ml, pANG II 13 +/- 2 pg/ml). In the hypertensive patients, binding capacity and affinity (Kd = 5.0 +/- 0.6 X 10(-10) M, 5.7 +/- 0.8 sites/cell) were similar to those in the normotensive subjects (Kd = 4.9 +/- 0.8 X 10(-10) M, 5.4 +/- 0.5 sites/cell). Changes in sensitivity to angiotensin II in essential hypertension may not be determined at receptor level. Angiotensin II receptors in platelets respond to changes in sodium intake like receptors in arterial muscle.

Adult↗

Angiotensin II effects on platelet function.

The effects of angiotensin II (ANG II) alone and in combination with other agonists on platelet aggregation, thromboxane B2 (TxB2) synthesis and cytosolic [Ca2+]i were investigated. Angiotensin II (10(-11)-10(-7) mol/l) alone had no direct effect on aggregation, TxB2 production or [Ca2+]i after short- (< 2 min) or long-term (30 min) incubation. In contrast, low concentrations of ANG II (10(-11) mol/l) enhanced adrenaline-induced platelet aggregation but high concentrations (10(-7) mol/l) had an inhibitory effect. Moreover, ANG II (10(-11)-10(-7) mol/l) augmented platelet responses to the TxA2 mimetic U44069. The facilitatory effect of ANG II on adrenaline-induced platelet aggregation was abolished by pretreatment of platelets with flurbiprofen. Thromboxane B2 synthesis by adrenaline-treated platelets was inhibited by ANG II. The results indicate that ANG II stimulation of agonist-induced platelet activation is due to potentiation of the effects rather than the synthesis of TxA2.

Angiotensin II↗

Receptors for angiotensin II on platelets from man.

Platelets were prepared from peripheral venous blood on iso-osmotic density gradients of Percoll, resulting in a good recovery of cells (50-80%) which were relatively free of contaminating blood cells (erythrocyte less than 0.1%, leucocyte less than 1%). At 22 degrees C, specific binding of 125I-labelled angiotensin II (300 pmol/l) was time and temperature dependent, saturable, reversible and linear with cell concentration. Scatchard analysis of saturation curves revealed a single class of binding sites with Kd 1.5 +/- 0.4 X 10(-10) mol/l and total binding capacity 6.3 +/- 1.2 receptors/platelet. Similar values (Kd 2.4 +/- 0.7 X 10(-10) mol/l and binding capacity 6.5 +/- 1.0 receptors/cell) were obtained by displacement analysis. From kinetic studies the forward and reverse rate constants were 3.1 X 10(8) mol min-1 l-1 and 3.6 X 10(-2)/min giving a Kd of 1.2 X 10(-10) mol/l. The relative binding potencies for angiotensin II and analogues were: [Sar1, Thr8]ANG II greater than ANG II greater than ANG III greater than [Sar1, Ala8]ANG II greater than ANG I. Incubation with an extracellular marker (51Cr-labelled EDTA) demonstrated that binding of angiotensin II to platelets was not due to free fluid endocytosis.

Adult↗