pituitrin and Coronary-Vasospasm

The obligatory role of the endothelium in relaxations of isolated coronary arteries to acetylcholine is explained by the release by endothelial cells of a labile vasodilator substance(s), endothelium-derived relaxing factor(s). Other neurohumoral mediators can evoke endothelium-dependent relaxations of coronary arteries. Of particular importance from the clinical point of view are thrombin, serotonin and adenine nucleotides. The latter are chiefly responsible for the endothelium-dependent relaxations evoked by aggregating platelets. The absence or the dysfunction of the endothelium may favour the occurrence of vasospasm.

Topics: Adenine Nucleotides; Animals; Blood Coagulation; Blood Vessels; Catecholamines; Coronary Vasospasm; Dogs; Endothelium; In Vitro Techniques; Muscle Relaxation; Muscle, Smooth, Vascular; Platelet Aggregation; Serotonin; Vasopressins

Topics: Blood Volume; Coronary Vasospasm; Heart Failure; Humans; Osmolar Concentration; Pressoreceptors; Prostaglandins E; Renin; Vascular Resistance; Vasopressins; Water-Electrolyte Balance

Cardioplegic arrest (CP) and cardiopulmonary bypass (CPB) are associated with vasomotor dysfunction of coronary arterioles in patients with diabetes (DM) undergoing cardiac surgery. We hypothesized that DM may up-regulate vasopressin receptor expression and alter the contractile response of coronary arterioles to vasopressin in the setting of CP/CPB.. Right atrial tissue samples of patients with DM and without (ND) (n = 8 in each group) undergoing cardiac surgery were harvested before and after CP/CPB. The isolated coronary arterioles (80-150 μm) dissected from the harvested right atrial tissue samples were cannulated and pressurized (40 mm Hg) in a no-flow state. The changes in diameter were measured with video microscopy. The protein expression/localization of vasopressin 1A receptors (V1A) and vasopressin 1B receptors (V1B) in the atrial tissue were measured by immune-blotting and immunohistochemistry.. CP/CPB and DM are both associated with up-regulation in V1 receptor expression/localization in human myocardium. Vasopressin may induce coronary arteriolar constriction via V1A. This alteration may lead to increased coronary arteriolar spasm in patients with DM undergoing CP/CPB and cardiac surgery.

Topics: Aged; Arterioles; Cardiopulmonary Bypass; Case-Control Studies; Coronary Artery Bypass; Coronary Vasospasm; Coronary Vessels; Diabetes Mellitus; Female; Heart Arrest, Induced; Humans; Male; Middle Aged; Receptors, Vasopressin; Signal Transduction; Up-Regulation; Vasoconstriction; Vasoconstrictor Agents; Vasopressins

We assessed the anti-anginal effects of cilnidipine in comparison with those of nicardipine and nifedipine (1 and 10 µg/kg, n = 6 for each drug) or vehicle (n = 6) by using the vasopressin-induced angina model of rats. The administration of vasopressin (0.5 IU/kg, i.v.) to the rats depressed the S-wave level of the electrocardiogram reflecting the presence of subendocardial ischemia, whereas it significantly increased the mean blood pressure, resulting in the decrease of the heart rate and the prolongation of the PR interval possibly through a reflex-mediated increase in vagal tone. Cilnidipine suppressed the vasopressin-induced depression of the S-wave level in a dose-related manner, which was not observed by nicardipine or nifedipine. In addition, the low dose of cilnidipine hardly affected the vasopressin-induced pressor response, but it attenuated the negative dromotropic effect, suggesting N-type Ca

Topics: Angina Pectoris; Animals; Blood Pressure; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, N-Type; Coronary Vasospasm; Coronary Vessels; Dihydropyridines; Disease Models, Animal; Dose-Response Relationship, Drug; Electrocardiography; Heart Rate; Male; Nicardipine; Nifedipine; Rats; Time Factors; Vasoconstriction; Vasodilator Agents; Vasopressins

The participation of vasopressin in the mechanisms of resistant hypertension is unclear. We compared plasma copeptin concentration, a surrogate marker for vasopressin secretion, between patients with resistant hypertension and those with controlled blood pressure (CBP), in a post hoc analysis of the Prise en charge de l'Hypertension Artérielle RESistante au traitement trial.. After 4-week treatment with irbesartan 300 mg/day, hydrochlorothiazide 12.5 mg/day, and amlodipine 5 mg/day (baseline), 166 patients were classified as having resistant hypertension (n = 140) or CBP (n = 26) by ambulatory BP monitoring. Patients with resistant hypertension were then randomized for 12 weeks of sequential nephron blockade (n = 74) or sequential renin-angiotensin system blockade (n = 66). Plasma copeptin concentration was measured at baseline and week 12 by immunoassay.. Baseline plasma copeptin concentration was positively associated with male sex, plasma osmolality, BP, and negatively with glomerular filtration rate. It was higher in the resistant hypertension than in the CBP group [geometric mean 5.7 (confidence interval 95% 5.1-6.4) vs. 2.9 (2.3-3.9) fmol/ml, adjusted P < 0.0001). The relationship between plasma copeptin concentration and urinary osmolality was similar in the two groups. At 12 weeks, plasma copeptin concentration in patients whose BP was controlled by sequential nephron blockade or sequential renin-angiotensin system blockade [6.8 (5.6-8.2) and 4.3 (3.0-5.9) fmol/ml, respectively) remained significantly higher than in patients with CBP at baseline (P < 0.0001 vs. both).. In patients with resistant hypertension, plasma copeptin concentrations were approximately two-fold higher than those of patients with CBP, after adjustment for plasma osmolality. This difference was not accounted for by renal resistance to vasopressin, suggesting a primary reset of osmostat.

Topics: Adult; Aged; Amlodipine; Antihypertensive Agents; Biomarkers; Biphenyl Compounds; Blood Pressure; Coronary Vasospasm; Diuretics; Female; Glomerular Filtration Rate; Glycopeptides; Humans; Hydrochlorothiazide; Hypertension; Irbesartan; Male; Middle Aged; Nephrons; Osmolar Concentration; Renin-Angiotensin System; Sex Factors; Tetrazoles; Vasopressins

The anticoronaryspastic and antibronchospastic activities of ethanolic and aqueous extracts of Valeriana officinalis L. roots were investigated in anaesthetized guinea-pigs and the results were correlated with the qualitative/quantitative chemical composition of the extracts in order to account for some of the common uses of this plant. The protective effects of orally administered ethanolic and aqueous extracts (50, 100 and 200 mg/kg) were evaluated against pitressin-induced coronary spasm and pressor response in guinea-pigs and were compared with those of nifedipine. Furthermore, the protective effects against histamine-induced and Oleaceae antigen challenge-induced bronchospasm were evaluated. Finally, the two valerian extracts were analytically characterized by qualitative and quantitative chromatographic analysis. The results showed that the two valeriana extracts possessed significant anticoronaryspastic, antihypertensive and antibronchospastic properties. These were similar to those exhibited by nifedipine and are due to the structural features of the active principles they contain. This study justifies the traditional use of this plant in the treatment of some respiratory and cardiovascular disorders.

Topics: Allergens; Animals; Antihypertensive Agents; Bronchial Spasm; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Coronary Vasospasm; Guinea Pigs; Histamine; Hypertension; Male; Oleaceae; Parasympatholytics; Plant Extracts; Plant Roots; Spectrophotometry, Ultraviolet; Ultrasonics; Valerian; Vasoconstrictor Agents; Vasopressins

We studied the antiischemic properties of fasudil, a Rho-kinase inhibitor, in conscious rabbits with coronary vasospasm induced by vasopressin and endothelin. Pretreatment with fasudil (0.3 and 3 mg/kg) attenuated the maximum elevation of the T-wave elicited by endothelin. Pretreatment with fasudil inhibited the T-wave elevation elicited by vasopressin. Fasudil and hydroxy fasudil, an active metabolite of fasudil, relaxed the endothelin-, U-46619-, 5-hydroxytryptamine- or histamine-induced contraction in swine coronary arterial strips. Fasudil and hydroxy fasudil significantly prevented the reduction in coronary flow by vasopressin in the Langendorff perfused rat heart. Fasudil was effective in protecting the heart against vasopressin and endothelin-induced myocardial ischemic change in conscious rabbits, and this beneficial effect can be attributed to its action of ameliorating the severe contraction of arteries. The inhibition of Rho-kinase may have implications for the development of novel therapeutic strategies for vasospastic angina in patients.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Angina Pectoris; Animals; Coronary Vasospasm; Disease Models, Animal; Dose-Response Relationship, Drug; Electrocardiography; Endothelins; Histamine; In Vitro Techniques; Intracellular Signaling Peptides and Proteins; Male; Protein Serine-Threonine Kinases; Rabbits; Rats; Rats, Wistar; rho-Associated Kinases; Swine; Time Factors; Vasodilation; Vasodilator Agents; Vasopressins

The question of whether the coronary vasospasm induced by intravenous administration of vasopressin produces any remodeling of the capillary network in the left ventricle was investigated. To this end, cardiac tissues obtained from vasopressin-injected rats were stained to allow capillary counting and for basic fibroblast growth factor (bFGF).. Nine male Donryu rats were divided into three groups that received, respectively, 0.25 ml of saline containing 0, 0.5, or 1.0 U/kg vasopressin injected into the tail vein once daily for 4 days. Rats were killed 30 days after the last injection. Two additional rats each received a single intravenous injection of 1.0 U/kg vasopressin and were killed 24 hours later. The left ventricles were removed and 16- or 10-micron frozen sections were cut for differential staining and distribution of bFGF, respectively. Differential staining was used to classify the capillary portions, and bFGF was identified by immunohistological staining.. Compared with the control group, total capillary density was increased in both vasopressin-treated groups, capillary to myocyte ratio was increased, and the capillary domain areas decreased in the three capillary portions. Arteriolar and intermediate capillary portions increased, while the venular capillary portion decreased. In rats killed 24 hours after vasopressin injection, a considerable amount of bFGF could be demonstrated immunohistochemically in the ventricular tissues, and the punctate distribution of bFGF was still found in rats killed 30 days after treatment.. A remodeling of capillary network which would increase the oxygen transport capacity to cardiac tissues was produced in left ventricular tissues by intravenous injection of vasopressin. bFGF located around capillaries and in the interstitial space may have been involved in the capillary remodeling.

Topics: Animals; Body Weight; Capillaries; Coronary Circulation; Coronary Vasospasm; Drug Administration Schedule; Heart Ventricles; Injections, Intravenous; Male; Organ Size; Rats; Rats, Inbred Strains; Vasopressins; Ventricular Function

In this study, the model of early myocardial infarction (EMI) was produced by legation of left anterior descending artery in rat. The artery spasm (CAS) was produced by external jugular vein injection of vasopressin (VP). Myocardium of apex and adjoining slice was used to make paraffin sections, then HE and LSAB-Mb staining were performed. Results showed: In 25 min after myocardial infarction, stretch-shape Mb depletion was observed in subendocardial myocardium of aortic ventricle's frontal wall. As the time of EMI prolonged, stretch-shape Mb depletion extended to epicardial layer. In CAS group, multiply, spotty Mb depletion was detected. There were more Mb depletion zones in right heart than that in left heart. The Mb depletion zones surrounded the CA or were like grape-clusters along the branches of one large CA. Thus, myocardial Mb depletion induced by EMI and CAS had different morphologic peculiarity. LSAB-Mb method could be hoped for the use of supplying objectively morphologic evidence to myocardial ischemia induced by CAS.

Topics: Animals; Coronary Vasospasm; Myocardial Infarction; Myocardium; Myoglobin; Rats; Rats, Wistar; Vasopressins

The aim of this study was to compare the antianginal effects of two compounds that release nitric oxide (NO) spontaneously, i.e. (+/-)-N-[(E)-4-ethyl-3-[(Z-hydroxyimino]-5-nitro-3-hexenyl] -3-pyridinecarboxamide (FR144420) and (+/-)-(E)-ethyl-2-[(E)-hydroxyimino] -5-nitro-3-hexenamide (FK409), in two different rat models of coronary vasospasm. In the rat methacholine-induced coronary vasospasm model, FR144420 suppressed the elevation of the ST segment dose dependently and significantly at 1.0 mg/kg, i.d. 185 min after its administration. FK409 suppressed the ST elevation only 5 min after its administration at 1.0 mg/kg, i.d. FR144420 and FK409 significantly decreased mean blood pressure at all doses tested only 5 min after their intraduodenal administration, but did not change heart rate at any time. Although the suppression of the ST elevation by FK409 had the same duration as its hypotensive effect, the FR144420-induced suppression of the ST elevation lasted longer than its hypotensive effect. In the rat vasopressin-induced coronary vasospasm model, FR144420 (32 mg/kg) significantly inhibited the depression of the ST segment both 60 min and 120 min after oral administration, whereas FK409 (32 mg/kg) significantly inhibited this ST depression only 60 min after oral administration. These data suggest that FR144420 inhibits coronary vasospasm for longer than FK409 does and particularly shows more prolonged antianginal effects than hypotensive effects in the methacholine-induced coronary vasospasm model. Thus FR144420 is expected to be a useful NO releaser for investigating the in vivo actions of NO.

Topics: Animals; Blood Pressure; Coronary Vasospasm; Electrocardiography; Male; Methacholine Chloride; Nicotinic Acids; Nitric Oxide; Nitro Compounds; Rats; Rats, Sprague-Dawley; Vasodilator Agents; Vasopressins

1. The preventive effects of monatepil, a new calcium antagonist with alpha 1-adrenoceptor blocking activity, on ischaemic electrocardiographic changes in rat models of vasospastic angina were evaluated and compared with those of the existing calcium antagonists (diltiazem, verapamil, nicardipine and nifedipine). 2. In order to assess the contribution of the alpha 1-adrenoceptor blocking action of monatepil to its anti-vasospastic action, the anti-ST depression effect of prazosin, an alpha 1-adrenoceptor blocker, was also examined. 3. Monatepil given orally (3-30 mg/kg) inhibited vasopressin (0.2 IU/kg, i.v.)-induced ST depression which is considered to indicate ischaemic electrocardiographic changes in a vasospastic angina. This effect of monatepil was more potent and long-lasting than that of diltiazem, and was similar to that of verapamil and nicardipine. At a dose of 30 mg/kg, monatepil produced a significant inhibition, even at 7 h after administration. 4. Monatepil given intravenously (0.3 mg/kg) exerted a significant inhibitory effect on methacholine (16 micrograms/kg, intracoronary arterial administration; i.c.a.)-induced ST elevation which seems to be caused by coronary vasospasm. This effect was more potent or equipotent to those of the existing calcium antagonists. 5. These results indicate that monatepil produces the preventive effect on the drug-induced ischaemic electrocardiographic changes in rats and suggest that monatepil may have potential for the treatment of vasospastic angina.

Topics: Administration, Oral; Animals; Blood Pressure; Calcium Channel Blockers; Coronary Vasospasm; Dibenzothiepins; Electrocardiography; Heart Rate; Injections, Intravenous; Male; Methacholine Chloride; Myocardial Ischemia; Piperazines; Prazosin; Rats; Rats, Sprague-Dawley; Rats, Wistar; Vasopressins

Studies were carried out to demonstrate the presence of the endothelium derived relaxing factor (EDRF) in coronary arteries in situ and the effect of hydroquinone on this factor. The studies revealed the presence of EDRF in coronary arteries of rabbit hearts remaining in situ. EDRF was inactivated by left atrial injection of hydroquinone. In situ constriction of coronary arteries by vasopressin was markedly increased following exposure to hydroquinone, and the dilatory response to acetylcholine was absent. The experiments confirm the presence of the endothelium derived relaxing factor in coronary arteries in situ and its inactivation by hydroquinone.

Topics: Animals; Arteries; Coronary Vasospasm; Coronary Vessels; Dose-Response Relationship, Drug; Endothelium; Hydroquinones; Image Processing, Computer-Assisted; Microscopy, Electron, Scanning; Nitric Oxide; Rabbits; Vasodilation; Vasodilator Agents; Vasopressins

Topics: Angina Pectoris; Animals; Beverages; Coronary Vasospasm; Plants, Medicinal; Rats; Vasopressins

We have studied the effects of 17 beta-estradiol on the left ventricular pressure and on the coronary perfusion pressure in isolated rabbit heart, in order to evaluate the action of this hormone on the myocardial contractility and on the coronary resistances. 17 beta-Estradiol has induced a negative inotropic effect starting from a concentration of 10(-6) M and a vasodilation starting from 10(-7) M when administered on a vasopressin-induced coronary spasm. These effects are not related to sex or to alpha-, beta-adrenergic, histaminergic, anaesthetic-like mechanisms, but seem to interfere with calcium transport.

Topics: Animals; Blood Pressure; Coronary Circulation; Coronary Vasospasm; Depression, Chemical; Estradiol; Female; Heart; Histamine; In Vitro Techniques; Isoproterenol; Male; Myocardial Contraction; Nifedipine; Nitroglycerin; Propafenone; Propiophenones; Propranolol; Rabbits; Vascular Resistance; Vasopressins