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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of sulfhydryl (SH) groups appears to be fundamental to nitrate-induced vasodilation and N-acetylcysteine (NAC), a sulfhydryl (SH)-donor substance, potentiates hemodynamic responsiveness to nitrates. We investigated the effect of simultaneous administration of NAC and isosorbide dinitrate (ISDN) on development of nitrate tolerance. In a double-blind, randomized, placebo-controlled cross-over study, seven patients with stable angina pectoris were treated for two 8-day periods with ISDN (40 mg four times daily, q.i.d.) together with NAC (controlled release 600 mg q.i.d.) or matching placebo. Bicycle exercise tests were performed before treatment was started, 1 h after treatment was started, and at day 8. After 8-day treatment with ISDN + placebo, responses determined by exercise testing were diminished as compared with responses obtained during acute therapy and did not differ from baseline values, suggesting development of tolerance to ISDN. During treatment with ISDN + NAC, time to 1-mm ST depression was significantly prolonged (441 +/- 44 vs. 381 +/- 40 s, mean +/- SEM) and total ST segment depression significantly reduced (1.9 +/- 0.7 vs. 3.5 +/- 0.8 mm) as compared with baseline values. The reduction in ST segment depression was significantly more pronounced during ISDN + NAC (46%) as compared with ISDN + placebo (23%). Although exercise time and time to angina pectoris were unaffected. NAC augmented the antiischemic effects of ISDN as assessed by ECG. This finding may suggest that development of nitrate tolerance is modified by chronic oral high-dose NAC administration.
J Cardiovasc Pharmacol 1991 Jun
PMID:Continuous oral N-acetylcysteine treatment and development of nitrate tolerance in patients with stable angina pectoris. 171 11

We report the effects of monitored smoking cessation on adrenergic regulation in chronic smokers. The beta 2 adrenoceptor density of mononuclear leukocytes (MNLs) and plasma catecholamines was analyzed before cessation and 2, 3, and 8 weeks after cessation. We found a progressive increase in beta-adrenoceptor density after smoking cessation. During smoking the beta-adrenoceptor density was 1.456 +/- 83 (mean +/- SEM) binding sites per cell (n = 10), whereas 3 weeks after cessation the density was 1,774 +/- 157 sites per cell (n = 10; p less than 0.05), and at 8 weeks, 1,900 +/- 227 sites per cell (n = 8; p less than 0.05), representing an overall increase of 23%. Smoking cessation had no effect on binding affinity nor on lymphocyte subgroup distribution. The density of MNL cell beta-adrenoceptors in age-matched nonsmoking men was higher, at 1,896 +/- 271 sites per cell, than that of the chronic smokers before cessation, 1,419 +/- 117 sites per cell (n = 14; p less than 0.01). Plasma epinephrine decreased as a result of cessation from 0.36 pmol/ml (0.26-0.44, 95% confidence interval; baseline) to 0.26 pmol/ml (0.20-0.32) at 8 weeks (p less than 0.05), and norepinephrine decreased from 2.09 pmol/ml (1.38-2.80) to 1.69 pmol/ml (1.14-2.24; p = 0.06). We conclude that stopping smoking progressively increases beta 2-adrenoceptor density on MNL cells. Eight weeks after cessation the adrenoceptor density reaches the corresponding level of nonsmokers. These reversible changes in adrenergic regulation after smoking cessation may be associated with the relatively rapid reduction in cardiovascular disease risk among ex-smokers.
J Cardiovasc Pharmacol 1991 Jun
PMID:Cigarette smoking alters sympathoadrenal regulation by decreasing the density of beta 2-adrenoceptors. A study of monitored smoking cessation. 171 16

In the present study the effects of alterations in extracellular magnesium concentration on spontaneous release of endothelium-derived relaxing factor (EDRF) and acetylcholine-, thrombin-, and calcium ionophore A23187-induced EDRF-dependent relaxation in isolated canine coronary arteries were determined. Increasing the extracellular magnesium concentration from the standard 1.2 to 2.4 mM did not alter the coronary contractile responses, while complete removal of extracellular magnesium resulted in an EDRF-dependent relaxation. The averaged percent relaxation of coronary arteries previously constricted with either prostaglandin F2 alpha, norepinephrine, or barium chloride was -75.9 +/- 4.4 (mean +/- SEM of 27 vessel segments), -43.1 +/- 4.9% (20 segments), and -25.8 +/- 6.9% (15 segments), respectively. Complete removal of extracellular magnesium also resulted in a slight but significant rightward shift of the concentration-response curves of acetylcholine- and thrombin-induced EDRF-dependent relaxation. The maximum relaxation was decreased to 86.5 +/- 1.7% and 69.5 +/- 4.6% of the control acetylcholine and thrombin relaxation, respectively. In contrast, the calcium ionophore A23187-induced EDRF-dependent relaxation was not altered following magnesium withdrawal, nor was the isoproterenol-induced endothelium-independent relaxation. These results suggest that extracellular magnesium exerts a direct inhibitory effect on the spontaneous release of EDRF and is apparently important for the expression of endothelium-dependent relaxation induced by acetylcholine and thrombin, but not calcium ionophore A23187, in canine coronary arteries.
J Cardiovasc Pharmacol 1991 Jun
PMID:Differential effects of magnesium on basal and agonist-induced EDRF relaxation in canine coronary arteries. 171 27

The effects of antihypertensive treatment with calcium antagonists or angiotensin-converting enzyme (ACE) inhibitors on the reversal of left ventricular hypertrophy and the left ventricular function in elderly hypertensive patients were examined. Twenty-four elderly hypertensive patients with cardiac hypertrophy, aged from 65 to 79 years (mean +/- SEM of 71 +/- 1 years), were treated with a calcium antagonist (nifedipine or nicardipine) or ACE inhibitor (captopril or enalapril) for 3 months. Thirteen patients had essential hypertension [EH: systolic blood pressure (SBP) greater than or equal to 160 mm Hg and diastolic blood pressure (DBP) greater than or equal to 90 mm Hg, aged 70 +/- 1 years] and 11 had isolated systolic hypertension (ISH:SBP greater than or equal to 160 mm Hg and DBP less than 90 mm Hg, aged 74 +/- 2 years). All patients underwent M-mode echocardiography to assess left ventricular mass index (LVMI) and left ventricular function (ejection fraction, EF) before and after 3 months of treatment. BP significantly decreased from 174 +/- 3/97 +/- 1 to 144 +/- 5/84 +/- 2 mm Hg in EH and from 167 +/- 3/82 +/- 2 to 144 +/- 4/74 +/- 2 mm Hg in ISH. The LVMI was also significantly reduced from 204 +/- 14 to 174 +/- 16 g/m2 in EH and from 179 +/- 14 to 156 +/- 12 g/m2 in ISH. EF showed no significant changes with treatment in either group. In elderly hypertensive patients, the antihypertensive treatment with calcium antagonist or ACE inhibitor reduced cardiac hypertrophy without any deterioration of left ventricular function in both essential hypertension and isolated systolic hypertension.
J Cardiovasc Pharmacol 1991
PMID:Effects of antihypertensive treatment on cardiac hypertrophy and cardiac function in elderly hypertensive patients. 171 72

Treatment of severe hypertension is beneficial, but reversibility of target-organ damage has not been characterized. Serial studies were performed in 15 patients with severe essential hypertension (age of 56 +/- 3 years, mean +/- SEM) treated for 1 year with 60 to 150 mg/day of continuous-release nifedipine; 3 patients required 50 mg of chlorthalidone/day to lower diastolic blood pressure (BP) to less than 95 mm Hg. Left ventricular (LV) structure and function was evaluated with two-dimensional-directed M-mode echocardiography, digitized from videotape and analyzed blindly. BP was markedly reduced from 194 +/- 8/115 +/- 4 to 146 +/- 4/88 +/- 14 mm Hg (p less than 0.0001) and maintained at this level for 1 year. Posterior wall and septal LV thickness, elevated at entry (12.9 +/- 0.1 and 13.4 +/- 0.1 mm), dropped steadily over 1 year into the normal range (10.0 +/- 0.03 and 11.2 +/- 0.1 mm, p less than 0.001). LV mass index, above 95% for normals at entry, decreased by 19% at 6 months (129 +/- 10 to 104 +/- 7 g/m2, p less than 0.01), and remained at this level at 1 year. LV fractional shortening rose steadily over 1 year from 34 to 42% (p less than 0.02). Atrial natriuretic peptide, which reflects LV filling pressures, was markedly elevated at entry, but was significantly reduced by 6 months (76 +/- 22 vs. 45 +/- 14 pg/ml, p less than 0.05). Sustained reduction of arterial BP with continuous-release nifedipine for 1 year normalizes LV mass, improves LV systolic function, and reduces circulating levels of atrial natriuretic peptide.
J Cardiovasc Pharmacol 1991
PMID:Effect of nifedipine GITS on left ventricular mass and diastolic function in severe hypertension. 171 75

Plasma insulin levels and the sensitivity of peripheral tissue to insulin (SI) have pathophysiological, therapeutic, and possibly also prognostic relevance. To investigate the effects of short-term selective alpha 1-adrenergic receptor blockade in nonobese normotensive humans on glucose and lipoprotein homeostasis, we assessed SI (determined by the minimal model method of Bergman), before and after glucose load plasma, glucose, and insulin levels, serum total triglycerides and lipoprotein cholesterol fractions, and some other variables in 20 healthy young men (26 +/- 1 years old, mean +/- SEM) during placebo and after 5 weeks of terazosin administration at a dose up to 10 mg once daily. Measurements were made after 3 days of standard diet (2,500 kcal/day, 45% carbohydrates, 40% fat, and 15% proteins) and after an overnight fast. Compared to placebo, terazosin decreased the upright systolic blood pressure (placebo vs. terazosin: 125 +/- 2 vs. 117 +/- 2 mm Hg, p less than 0.05) and increased supine (63 +/- 2 vs. 70 +/- 1 beats/min, p less than 0.05) and upright (77 +/- 2 vs. 88 +/- 2 beats/min, p less than 0.01) heart rates, while the body weight was unaltered. Terazosin did not significantly modify fasting plasma glucose (5.08 +/- 0.09 vs. 5.23 +/- 0.08 mmol/L, respectively), or insulin (8.9 +/- 0.5 vs. 8.6 +/- 0.6 microU/ml), SI (14.3 +/- 1.8 vs 11.8 +/- 1.5 x 10(-4)/min/microU/ml), the areas under the insulin or glucose curves, serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1991 Jul
PMID:Postsynaptic alpha 1-blockade with terazosin does not modify insulin sensitivity in nonobese normotensive subjects. 171 77

To elucidate the mechanism of acute contractile failure induced by adriamycin, the intracellular concentrations of free calcium ([Ca2+]i) and energy-related phosphate compounds were determined in isolated ferret hearts. The time-averaged [Ca2+]i was measured at 10 min resolution using fluorine nuclear magnetic resonance (NMR) spectroscopy and the NMR-sensitive Ca2+ indicator 5F-BAPTA. [Ca2+]i significantly increased from a control of 381 +/- 66 nM (mean +/- SEM, N = 5) to 789 +/- 171 nM during 30 min of perfusion with adriamycin (30 mg/L), and remained elevated for at least 30 min after washout. The isovolumic LV pressure decreased to 80.7 +/- 8.9% of control (N = 12, p less than 0.05) and did not recover after washout. Intramyocardial contents of energy-related phosphates were determined by phosphorus NMR spectroscopy in seven other hearts. No significant change in myocardial energy metabolism was observed during adriamycin exposure and after washout; inorganic phosphate did not increase, and phosphocreatine and ATP did not decrease. These results indicate that Ca overload induced by adriamycin is associated with acute contractile failure. Adriamycin has been reported to inhibit Na-Ca exchange and to affect the gating of Ca2+ release channels in sarcoplasmic reticulum. Whatever the cause of the calcium overload, the fact that dysfunction persists as an aftereffect of adriamycin is consistent with the hypothesis that calcium overload, in the absence of ischemia, can leave behind long-lasting contractile dysfunction.
J Cardiovasc Pharmacol 1991 Sep
PMID:Alterations of intracellular calcium homeostasis and myocardial energetics in acute adriamycin-induced heart failure. 172 Aug 44

We screened the antiischemic, hemodynamic, and inotropic effects of different dosages of the new calcium channel blocker Ro 40-5967 in 65 patients with stable effort-induced angina pectoris. In a double-blind way, patients were randomized to recieve a single oral dose of 50, 100, or 200 mg Ro 40-5967 or placebo, given as a drinking solution. Left ventricular ejection fraction (LVEF), blood pressure (BP), and heart rate (HR) were measured at rest and during a supine bicycle exercise test on day 0 (baseline) and 2 h after drug intake on day 1. Twenty-four hours later, the bicycle exercise test was repeated. Ro 40-5967 improved exercise duration and resting LVEF. After 200 mg, exercise time increased significantly from 8.4 +/- 0.8 min (mean +/- SEM) to 9.6 +/- 0.7 min (p = 0.018), and LVEF at rest increased from 54.5 +/- 2.2 to 58.1 +/- 2.6% (p = 0.045). Time to 0.1 mV ST-segment depression increased significantly from 4.3 +/- 0.8 to 5.5 +/- 0.9 min in the 100-mg group (p = 0.013) and from 4.3 +/- 1.3 to 5.4 +/- 1.5 min in the 200-mg group (p = 0.027). Maximum ST-segment depression decreased significantly at all dose levels (p = 0.01), with the maximum decrease noted in the 200-mg group (from 0.21 +/- 0.03 to 0.15 +/- 0.02 mV, p = 0.004). BP, HR, and rate-pressure product did not change significantly at rest or at maximum exercise. A single dose of Ro 40-5967 has antiischemic properties in patients with stable angina pectoris, with maximum effects obtained after 200 mg. No signs of negative inotropy were noted, and the drug was well tolerated.
J Cardiovasc Pharmacol 1991 Nov
PMID:Lack of negative inotropic effects of the new calcium antagonist Ro 40-5967 in patients with stable angina pectoris. 172 72

The effect of enalapril and angiotensin II on junctional conductance (gj) of isolated rat heart cell pairs was investigated. It was found that enalapril (1 micrograms/ml) increases gj by 106 +/- 3.1% (SEM) (n = 20) within 4 min. The effect of enalapril on gj was not suppressed by propranolol (10(-6) M) or by a cAMP-dependent protein kinase inhibitor. Angiotensin II (1 micrograms/ml) reduced gj by 55%. These observations might indicate that an intrinsic renin-angiotensin system in heart is involved in the control of gj in cardiac muscle.
J Cardiovasc Pharmacol 1991 Oct
PMID:Enalapril, an inhibitor of angiotensin converting enzyme, increases the junctional conductance in isolated heart cell pairs. 172 43

Thirty-six hypertensive patients with impaired renal function entered a long-term study to assess the safety of perindopril. There were 28 men and 8 women of mean age 57.1 +/- 2.0 years (mean +/- SEM). The duration of documented hypertension was 7.3 +/- 1.2 years. Perindopril was given orally in single daily doses. The initial dosage was chosen according to the degree of renal function impairment: 29 patients received 4 mg o.d. [creatinine clearance (Clcr), 42.2 +/- 3.2 ml.min-1] and 7 patients received 2 mg o.d. (Clcr, 22.3 +/- 3.1 ml.min-1). Patients in whom blood pressure was not controlled had their dose doubled and then, if necessary, an additional diuretic therapy was added at subsequent visits. Six patients were withdrawn for adverse events (myocardial infarction, pneumonia, leucopenia in a patient who had lupus, diabetes mellitus, skin rash, epigastric pain), two patients were withdrawn for poor compliance, and three for personal convenience. The mean duration of treatment was 10.2 months with a range of 3-12 months (excluding one patient who died from myocardial infarction in the first days of the study and was not included in the analysis). Systolic and diastolic blood pressure decreased significantly (from 170.5/100.6 +/- 3.4/1.8 mm Hg to 151.8/88.8 +/- 3.0/1.7 mm Hg, n = 35, p less than 0.001). Baseline and final values of plasma creatinine (from 223.7 +/- 22.7 to 234.7 +/- 28.5 mumols/l), Clcr (42.5 +/- 3.2 to 45.7 +/- 4.6 ml.min-1), and kalemia (from 4.4 +/- 0.1 to 4.7 +/- 0.1 mmol/L) were not statistically different.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1991
PMID:Long-term tolerance of perindopril in hypertensive patients with impaired renal function. 172 1


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