cyclic-gmp and Coronary-Vasospasm

Topics: Acetylcholine; Coronary Vasospasm; Cyclic GMP; Ergonovine; Guanosine Triphosphate; Guanylate Cyclase; Humans; Nitric Oxide

Most patients with vasospastic angina who have no significant organic coronary arterial stenosis are well controlled by medical therapy and the prognosis is almost satisfactory. Calcium channel (Ca) blockers are used as the first choice and effective agents for vasospastic angina pectoris. However, they do not always work well. Some uncontrolled coronary vasospasms would happen to cause prolonged occlusion of coronary artery resulting in myocardial infarction, life-threatening arrhythmias and sudden death. Therefore, it is very important to pay attention to such a refractory coronary spasm and choose the most effective agent out of Ca blockers for the treatment of each patient with vasospastic angina attacks. This study was designed to evaluate the anti-vasospastic efficacy of benidipine, a long acting dihydropyridine (DHP) Ca blocker, in patients with other Ca blockers-resistant angina.. Patients treated with diltiazem but not enough to control angina attacks were enrolled in the present study. Treatment with diltiazem (CAS 33286-22-5, 42399-41-7) was changed to treatment with benidipine (CAS 91599-74-5) and the parameters such as angina frequency, duration, blood pressure, heart rate, electrocardiogram and hematological parameters (serum NO(x), plasma cGMP) were measured and compared.. Fifteen patients with vasospastic angina were enrolled. After switching from diltiazem to benidipine, angina attacks were completely disappeared in six patients. Although the frequency was not decreased, the average duration of attacks was shorter than before in three patients. Four patients did not improve and two patients obviously worsened. In the improved nine patients, serum nitrite/nitrate (NO(x)) levels showed a significant increase from 37.6 +/- 15.3 to 54.5 +/- 26.7 pmol/L (p < 0.05) and cGMP levels subsequently elevated from 2.2 +/- 0.8 to 2.5 +/- 0.6 micromol/L (p = 0.05) after benidipine therapy started. Adverse effects such as hypotension and bradycardia were not observed.. This study suggests that benidipine may be helpful in Japanese patients with vasospastic or variant angina pectoris, if diltiazem was not successful.

Topics: Aged; Angina Pectoris; Blood Pressure; Calcium Channel Blockers; Coronary Vasospasm; Cyclic GMP; Dihydropyridines; Diltiazem; Female; Heart Rate; Humans; Male; Middle Aged; Nitric Oxide; Treatment Failure; Treatment Outcome; Vasodilator Agents

It has been shown that there is the supersensitivity of the dilator effect of nitrovasodilators in the coronary arteries of patients with coronary spastic angina. This study was aimed to elucidate its mechanism(s) by examination of dilator response of spastic coronary arteries to atrial natriuretic peptide (ANP), which is known to dilate arteries by the same final common pathway through cyclic guanosine monophosphate (cGMP) as nitrovasodilators. Effects of infusion of nitroglycerin and ANP on epicardial coronary diameter of left coronary arteries were thus examined by quantitative coronary angiography in 20 patients with coronary spastic angina, who had spasm in left coronary arteries, and in 27 control subjects. Dilator response of coronary diameter to intracoronary infusion of ANP (0.5 microgram/kg) was found to be comparable between spastic coronary arteries and control arteries, whereas dilator response to nitroglycerin (250 micrograms) was enhanced in the spastic arteries compared with control arteries. The results indicate that spastic coronary arteries exhibit supersensitive dilator response to nitroglycerin but not to ANP. There is a possibility that dilator response to cGMP may be comparable between spastic and control coronary arteries and that soluble guanylate cyclase activity and/or conversion of nitric oxide bio-activity from nitroglycerin may be enhanced in spastic coronary arteries.

Topics: Adult; Aged; Angina Pectoris; Atrial Natriuretic Factor; Biological Availability; Coronary Angiography; Coronary Vasospasm; Coronary Vessels; Cyclic GMP; Diltiazem; Female; Guanylate Cyclase; Humans; Injections, Intra-Arterial; Male; Middle Aged; Nitric Oxide; Nitroglycerin; Vasodilator Agents

Alcohol is known to sometimes cause coronary spasm, the mechanism of which is still unknown. The authors monitored changes in plasma levels of prostanoids (thromboxane [TX B2], 6-keto prostaglandin F1 alpha [PGF1 alpha]), catecholamines (CA), serotonin (5-HT), cyclic nucleotides (cyclic adenosine monophosphate--cAMP, cyclic guanosine monophosphate--cGMP), and platelet aggregation after alcohol ingestion (Japanese rice wine 400 mL) in 8 patients with alcohol-induced variant angina and 8 healthy men as controls. Coronary spasm was confirmed to have been induced in 4 patients nine hours after alcohol challenge (VA[+]), when their plasma ethanol levels had already returned to a null level. Neither CA nor 5-HT levels showed any change after alcohol ingestion either in patients or controls, though controls showed high levels of CA during alcohol ingestion. TX B2 in VA(+) patients increased gradually after alcohol ingestion to reach up to a statistically significantly high level just before attack, as compared with those of controls and VA(-) patients, who, on the contrary, did not show such changes. The levels of 6-keto PGF1 alpha, however, which were significantly lower in patients than in controls before the test, exhibited a gradual increase in VA(+) patients in parallel with the increase in TX B2. No significant changes in cAMP levels between either controls or patients were present. On the contrary, cGMP levels had a gradual decrease in patients after alcohol ingestion. Especially six hours after alcohol ingestion, cGMP levels in VA(+) patients decreased so much as to make a statistically significant difference, as compared with the level in controls. Platelet aggregability in controls showed a decrease after alcohol ingestion, in spite of no change or even increase in patients. These data suggest that low levels of PGF1 alpha and the decrease of cGMP levels from alcohol ingestion play important roles in the mechanism of coronary spasm induced by alcohol ingestion.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Alcohol Drinking; Coronary Angiography; Coronary Vasospasm; Cyclic AMP; Cyclic GMP; Electrocardiography; Epinephrine; Ethanol; Humans; Male; Middle Aged; Norepinephrine; Platelet Aggregation; Serotonin; Thromboxane B2; Wine

Atrial natriuretic peptide (ANP) is reported to dilate a major coronary artery in both experimental animals and humans. Spasm of a major coronary artery is the cause of variant angina pectoris and can be induced by hyperventilation. The effect of the ANP infusion on anginal attack induced by hyperventilation was studied in patients with variant angina pectoris. The study was performed in the early morning on 3 consecutive days in 11 patients with variant angina pectoris in whom the attacks were reproducibly induced by hyperventilation. On days 1 and 3 (saline solution infusion), and day 2 (ANP infusion), hyperventilation was started 14 minutes after beginning infusion of ANP (0.1 microgram/kg/min) or saline solution for 6 minutes. The attacks were induced in all 11 patients by hyperventilation on days 1 and 3. However, the attacks were not induced in any patient on day 2 of the ANP infusion. The plasma ANP level increased from 33 +/- 7 pg/ml to the peak level of 2,973 +/- 479 pg/ml (p < 0.01) at the end of the ANP infusion, and the plasma level of cyclic guanosine monophosphate (cGMP) increased from 5 +/- 1 pmol/ml to the peak level of 58 +/- 6 pmol/ml (p < 0.01) 5 minutes after the ANP infusion. The plasma levels of ANP and cGMP did not change after hyperventilation on days 1 and 3. It is concluded that the ANP infusion suppresses the attacks induced by hyperventilation in patients with variant angina pectoris, and cGMP is related to the mechanisms of suppression of the attacks.

Topics: Adult; Aged; Angina Pectoris, Variant; Atrial Natriuretic Factor; Carbon Dioxide; Coronary Vasospasm; Cyclic GMP; Electrocardiography; Female; Humans; Hydrogen-Ion Concentration; Hyperventilation; Infusions, Intravenous; Male; Middle Aged; Oxygen; Radioimmunoassay

Topics: Acetylcholine; Animals; Calcium; Cerebral Arteries; Coronary Vasospasm; Coronary Vessels; Cyclic GMP; Humans; Ischemic Attack, Transient; Nitric Oxide; Oxyhemoglobins

Plasma levels of cyclic nucleotides were determined by radioimmunoassay in patients with (1) angina-like chest pain and normal coronary arteries (suspected spasm angina), (2) exercise-induced angina, and (3) heart diseases other than angina pectoris, as well as in (4) normal subjects. The concentration of cyclic GMP in plasma was significantly lower (by at least three-fold) in patients with suspected spasm angina, as compared with the other groups. No statistically significant difference in the plasma levels of cAMP was observed between the different patient groups. The low cGMP levels in plasma from patients with angina-like chest pain and normal coronary arteries might be an indication of a defect in the vasculature, making it more sensitive to contractile stimuli.

Topics: Adult; Angina Pectoris; Coronary Angiography; Coronary Disease; Coronary Vasospasm; Cyclic AMP; Cyclic GMP; Female; Humans; Male; Middle Aged