Influence of dexamethasone on the responses of isolated coronary arteries to adrenaline

The effect of Dexamethasone on the adrenaline-induced relaxation was studied in vitro. Relaxation of response to adrenaline increased by Dexamethasone. We suggest that the Dexamethasone influence depends on inhibition of Catecol-O-methyl transferase (COMT).     

Melatonin potentiates contractile responses to serotonin in isolated porcine coronary arteries

The present study was designed to determine the effects of melatonin on coronary vasomotor tone. Porcine coronary arteries were suspended in organ chambers for isometric tension recording. Melatonin (10(-10)-10(-5) M) itself caused neither contraction nor relaxation of the tissues. Serotonin (10(-9)-10(-5) M) caused concentration-dependent contractions of coronary arteries, and in the presence of melatonin (10(-7) M) the maximal response to serotonin was increased in rings with but not without endothelium. In contrast, melatonin had no effect on contractions produced by the thromboxane A(2) analog U-46619 (10(-10)-10(-7) M). The melatonin-receptor antagonist S-20928 (10(-6) M) abolished the potentiating effect of melatonin on serotonin-induced contractions in endothelium-intact coronary arteries, as did treatment with 1H-[1, 2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10(-5) M), methylene blue (10(-5) M), or N(G)-nitro-L-arginine (3 x 10(-5) M). In tissues contracted with U-46619, serotonin caused endothelium-dependent relaxations that were inhibited by melatonin (10(-7) M). Melatonin also inhibited coronary artery relaxation induced by sodium nitroprusside (10(-9)-10(-5) M) but not by isoproterenol (10(-9)-10(-5) M). These results support the hypothesis that melatonin, by inhibiting the action of nitric oxide on coronary vascular smooth muscle, selectively potentiates the vasoconstrictor response to serotonin in coronary arteries with endothelium.     

Influence of pyridoxal-5'-phosphate on responses of isolated coronary arteries to noradrenaline, in the presence of pyrogallol

The effect of PLP on the noradrenaline-induced relaxation of coronary arteries was studied in vitro, after known inhibitor of COMT, Pyrogallol. Relaxation of response to noradrenaline were increased by PLP. Pyrogallol potentiated responses of coronary strips to noradrenaline and also reduced or abolished the enhancing effects of PLP. It is concluded that PLP enhances the response of coronary smooth muscle to noradrenaline by inhibiting a enzymatic pathway for the inactivation of catecolamines.     

Extravascular pressure modulates responses of isolated rat coronary arteries to vasodilator, but not vasoconstrictor, stimuli

The aims of the study were to investigate whether elevated extravascular pressure modulates responses of isolated rat coronary arteries to constrictor and dilator stimuli. Isolated segments of rat coronary artery were mounted in a modified pressure myograph system that allowed independent modulation of both intra- and extravascular pressures. The influence of elevated extravascular pressure on stable levels of myogenic tone and on responses to vasoconstrictor and vasodilator stimuli was investigated at constant overall transmural pressures. Stable levels of myogenic tone were independent of the relative levels of intra- and extravascular pressure, as were responses to depolarization and to addition of the thromboxane agonist U-46619. Elevating extravascular pressure, however, significantly reduced dilatory responses to introduction of intraluminal flow and to addition of endothelium-dependent and endothelium-independent vasodilatory agonists. These results support the notion that elevated extravascular pressure may attenuate responses of coronary arteries to a variety of dilatory stimuli. This finding may be of relevance to cardiac disorders associated with elevated ventricular pressures.     

Influence of desoxycorticosterone on the response of calf coronary artery strips to adrenaline

The effect of desoxycorticosterone on the adrenaline-induced relaxation of coronary arteries was studied "in vitro". It resulted that the effect of adrenaline was enhanced by desoxycorticosterone. It is concluded that desoxycorticosterone potentiates the effects of adrenaline by inhibiting its inactivation by Catechol-O-methyltransferase.     

Influence of variations of Ca++ on responses of segments of the isolated coronary artery to acetylcholine

The effect of external calcium concentration on the Ach-induced contraction of coronary arteries was studied in vitro. It resulted that the effect of Ach was enhanced by the increase, or reduced by the decrease of calcium concentration. It is concluded that, as it was known for the intestinal smooth muscle, also for the smooth muscle of the coronary arteries, the contractile effect of Ach is dependent on the calcium of the medium.     

Influence of desoxycorticosterone on the reaction of isolated segments of coronary arteries to noradrenaline in the presence of pyrogallol

The effect of the desoxycorticosterone on the noradrenaline-induced relaxation of coronary arteries waw studied in vitro, after a known inhibitor of COMT, pyrogallol. Relaxation induced by noradrenaline was enhanced by desoxycorticosterone. Relaxation in response to noradrenaline was increased by desoxycorticosterone. Pyrogallol potentiated the responses of coronary strips to noradrenaline and also reduced or abolished the enhancing effects of desoxycorticosterone. It is concluded that desoxycorticosterone enhances the reponse of coronary smooth muscle to noradrenaline by inhibiting and enzymatic pathway for the inactivation of catecolamines.     

Flow and pressure responses of coronary arteries and veins to vasodilating agents

The response to a bolus injection of nitroglycerine, adenosine, nifedipine, and dipyridamole of the canine systemic as well as coronary artery and venous circulations was observed and contrasted. Particular attention was paid to the time of change of pressures and flows and to changes in oxygen extraction by the myocardium induced by the pharmacological agents. The dosages of vasodilators used were selected so that no significant change in aortic blood flow occurred. Nitroglycerine and adenosine caused a rapid and similar vasodilation in the coronary circulation. Oxygen extraction was not altered by nitroglycerine, but was decreased by adenosine. The onset time of the vasodilation produced by either nifedipine or dipyridamole was similar, but the time to peak action was much slower for dipyridamole. As well, the effect of dipyridamole on intramyocardial and left intraventricular pressures was more delayed than that following the injection of the other agents. Oxygen extraction was reduced by nifedipine and dipyridamole. These results indicate that pharmacological vasodilating agents can affect coronary arteries, coronary veins, and myocardial oxygen extraction differently.     

Influence of hydrocortisone on the response to noradrenaline of segments of isolated coronary arteries in the presence of a beta-adrenergic blocking agent

The effect of hydrocortisone on the noradrenaline-induces contraction, after propranolol, was studied in vitro. Contraction of response to noradrenaline were increased by hydrocortisone. We suggest that the hydrocortisone influence depends on inhibition of catecol-O-metiltransferase (COMT).     

Heterogeneity in responses of isolated monkey arteries and veins to atrial natriuretic peptide

Regional differences in responses of isolated monkey arteries and veins to atrial natriuretic peptide were investigated by recording isometric tension. Addition of atrial natriuretic peptide (4 X 10(-12) to 4 X 10(-8) M) produced a concentration-dependent relaxation in isolated monkey arteries and veins. No significant difference was observed between the responses to rat and human atrial natriuretic peptides. A marked heterogeneity in responses to rat atrial natriuretic peptide, however, was observed in arterial preparations. The decreasing order of the response was as follows: renal greater than pulmonary greater than femoral = mesenteric greater than coronary greater than middle cerebral greater than basilar arteries. A heterogeneity in the relaxation produced by atrial natriuretic peptide was also observed in monkey veins. The decreasing order of the response was as follows: pulmonary greater than mesenteric = portal greater than femoral greater than renal = inferior caval veins. On the other hand, 10(-5) M sodium nitroprusside caused a maximal relaxation in all monkey arteries and veins used. In the middle cerebral, basilar, and coronary arteries, the relaxant effects of rat atrial natriuretic peptide on KCl-induced contraction were significantly smaller than those on the preparations contracted by an agonist such as prostaglandin F2 alpha. These results suggest that there exist profound regional vasorelaxant selectivities of atrial natriuretic peptide in isolated monkey arteries and veins.     

Influence of desoxycorticosterone on the response of coronary artery segments to adrenaline in the presence of pyrogallol

The effect of desoxycorticosterone on the adrenaline-induced relaxation of coronary arteries was studied in vitro, after a known inhibitor of COMT, pyrogallol. Relaxation induced by adrenaline was enhanced by desoxycorticosterone. Relaxation in response to adrenaline was increased by desoxycorticosterone. Pyrogallol potentiated the responses of coronary strips to adrenaline and also reduced or abolished the enhancing effects of desoxycorticosterone. It is concluded that desoxycorticosterone enhances the response of coronary smooth muscle to adrenaline by inhibiting an enzymatic pathway for the inactivation of catecholamines.     

Interleukin 6 polymorphism corresponds to the number of severely stenosed coronary arteries

IL6 gene promoter polymorphisms may influence the outcome of cardiovascular diseases. The aim of our study was to find out whether the -174G>C polymorphism, as well as the IL6 secretory profile, may be linked to the number of severely (> or = 75%) occluded coronary arteries in patients with advanced coronary heart disease (CHD). Three hundred and twenty patients awaiting elective coronary artery bypass grafting were enrolled into the study. Blood was taken the day before surgery. The PCR-RFLP method was used for IL6 gene polymorphism analysis. Spontaneous IL6 release was measured by bioassay in supernatants of whole blood cell cultures (WBCC) incubated for 24 h and 48 h. We found that significantly more patients with triple vessel disease were found within the -174GG group as compared to the -174GC and CC genotype carriers. The highest IL6 serum levels were found in the -174GG and the lowest in the -174CC genotype patients. Spontaneous in vitro IL6 secretion appeared to be significantly higher at all time points in the -174GG as compared to the CC and GC genotype carriers. The serum concentration of IL6 and the spontaneous IL6 secretion were directly related to the number of obstructed coronary vessels. Our results emphasize the role of IL6 as an important, non-classical risk factor predicting the number of severely affected coronary vessels.     

Acute responses to phytoestrogens in small arteries from men with coronary heart disease

The aim of this study was to investigate acute vasodilator responses to phytoestrogens and selective estrogen receptor-alpha (ERalpha) agonist in isolated small arteries from men with established coronary heart disease (CHD) and with a history of myocardial infarction versus healthy male control subjects. As to methodology, small arteries obtained from subcutaneous fat biopsies and mounted on a wire myograph were preconstricted with norepinephrine, and dilator responses to increasing nanomolar-micromolar concentrations of the phytoestrogens resveratrol and genistein (predominantly ERbeta agonists) and to propyl-[1H]-pyrazole-1,3,5-triyl-trisplenol (PPT, a selective ERalpha agonist) were determined. These were compared with responses to reference compound 17beta-estradiol (17beta-E2). Concentration-response curves were constructed before and after nitric oxide (NO) synthase inhibition with Nomega-nitro-L-arginine methyl ester. As a result, relaxation induced by the investigated compounds was similar in men with CHD and control men, but in both groups PPT and genistein-induced relaxation was greater than that of resveratrol and 17beta-E2. NO contributed to both phytoestrogens and PPT-induced relaxation but not to 17beta-E2 responses in arteries from control men. This NO-mediated component of relaxation was absent in arteries from men with established CHD. In conclusion, phytoestrogens, at concentrations achievable by ingestion of phytoestrogen-rich food products, evoke dilatation ex vivo of small peripheral arteries from normal men and those with established CHD. The contribution of NO to dilatory responses by these compounds is pertinent to arteries from control males, whereas other NO-independent dilatory mechanism(s) are involved in arteries from CHD.     

Action of agonists and antagonists on adrenergic receptors in isolated porcine coronary arteries

The adrenergic receptors of porcine coronary arteries were investigated in helically cut strips of small (less than or equal to 0.5 mm outer-diameter (od), medium (0.8-1.2 mm od), large (1.5-2.5 mm od), and very large (greater than 4 mm od) coronary arteries. Both the beta1 agonist dobutamine and the beta2 agonist terbutaline relaxed coronary arteries partially contracted by 25 mM of KCl. Dobutamine contracted small coronary arteries at 10(-5) M concentrations, then relaxed them at 10(-4) M. The beta1-adrenoceptor antagonist metoprolol contracted coronary arteries relaxed by either dobutamine or terbutaline, but the beta2 antagonist H35/25 did so only in high and probably nonselective concentrations. Alpha1-adrenoreceptor stimulating concentrations of phenylephrine did not contract any of the arteries. Metoprolol and high concentrations of H35/25 further contracted large coronary arteries partially contracted by 25 mM potassium. These contractions were blocked by verapamil and papaverine but not by atropine, phentolamine, yohimbine, mepyramine, or methysergide. This seems to indicate that beta-adrenergic receptors in porcine coronary arteries are beta1-receptors, or closely resemble beta1-receptors. They differ from many other beta1-receptors, however, in that they are stimulated by terbutaline. Alpha1 adrenoreceptors seem not to be present in these porcine coronary arteries to a significant extent. Metoprolol and high concentrations of H35/25 have a direct contractile effect in large porcine coronary artery that is not mediated by alpha-adrenergic, muscarinic, histaminergic, or serotonergic receptors but requires verapamil-sensitive calcium.     

Retention of endothelium-dependent vasodilatory responses in canine coronary arteries following cryopreservation

In the present study, the cryoprotective effect of dimethyl sulfoxide (Me2SO) and fetal calf serum (FCS) on coronary endothelium and endothelium-dependent relaxation (EDR) responses was studied in isolated canine coronary arteries following cryostorage at -75 degrees C. Compared to the freshly isolated coronary arteries, the EDR responses to acetylcholine, thrombin, and calcium ionophore were not significantly altered following 1 day storage at -75 degrees C in the presence of 1.8 M Me2SO and 20% FCS. Prolonged cold storage to 7 days, however, resulted in a slight, but significant, rightward shift of the concentration-response curves of acetylcholine and thrombin, but not calcium ionophore. The maximum relaxant response after 7-day cryostorage was 80 to 85% of fresh controls. Omission of FCS from the cryostorage incubation medium further accentuated the loss of EDR responses to all three endothelium-dependent vasodilators tested. Scanning electron microscopic examinations of the intimal surface of the Me2SO and FCS cryostored canine coronary arteries confirmed the preservation of intimal endothelial cells following 1 or 7 days of storage at -75 degrees C, while significant patches of loss of endothelial cells were observed in the arteries cryostored only in the presence of Me2SO. No significant inhibitory effect of cryostorage was observed for the direct, endothelium-independent relaxation induced by isoproterenol, regardless of the presence or absence of FCS. These results demonstrate that slow freezing of canine coronary arteries to -75 degrees C in Krebs-Henseleit solution containing Me2SO and FCS provides good preservation of the vascular smooth muscle function and endothelium-dependent vasodilatory responses.     

Inhibitory effect of methergoline on serotonin induced contraction of isolated strips of coronary arteries

Metergoline (antiserotonin drug) prevents the contraction induced by serotonin on strips of isolated coronary arteries. Moreover when metergoline is added at the maximal contraction, it induces relaxation of the vascular smooth muscle preceeded by a brevious phase of contraction.     

Kinins mediate kallikrein-induced endothelium-dependent relaxations in isolated canine coronary arteries.

ACE inhibitors elicit the release of endothelium-derived relaxing factors in perfused isolated canine arteries (Mombouli and Vanhoutte, J. Cardiovasc. Pharmacol. 1991, 18: 926-927); this action is antagonized by bradykinin-receptor antagonists suggesting that it is mediated by local kinin generation. The effects of exogenous tissular kallikrein (porcine) were examined in vitro in the isolated canine coronary artery. Isometric tension was measured in blood vessel rings (with and without endothelium) contracted with prostaglandin F2 alpha. The kallikrein elicited relaxations in rings with, but not in those without, endothelium. This response was augmented by the angiotensin converting enzyme inhibitor perindoprilat, and it was antagonized by the selective B2-kinin receptor antagonist HOE 140 and aprotinin, an inhibitor of tissular kallikrein. These data suggest that in the canine coronary artery, kallikrein causes relaxations that may be mediated by kinins generated from endogenous kininogens present in the vascular wall.