Comparison of the effects of forskolin and isoproterenol on cyclic AMP levels and tension in bovine coronary artery

1983 ◽  
Vol 61 (10) ◽  
pp. 1202-1205 ◽  
Author(s):  
Raju V. K. Vegesna ◽  
Jack Diamond

The effects of isoproterenol and forskolin on cyclic AMP levels and tension were compared in helical strips of bovine coronary artery. Both compounds produced time- and dose-dependent increases in cyclic AMP levels and both compounds relaxed potassium-contracted arteries. However, in contrast to the results with isoproterenol, cyclic AMP elevation and relaxation were not well correlated at lower concentrations of forskolin. For example, 0.1 μM forskolin increased cyclic AMP levels in the arteries by approximately 5.5-fold but did not relax the muscles. A smaller elevation of cyclic AMP produced by 1.0 μM isoproterenol, on the other hand, was accompanied by an almost complete relaxation of the arteries. These results suggest that either cyclic AMP is not responsible for the relaxation caused by these agents, or some form of functional compartmentalization of cyclic AMP exists in this tissue.

2019 ◽  
Vol 34 (1) ◽  
pp. 24-32
Author(s):  
Y. Y. Vecherskiy ◽  
D. V. Manvelyan ◽  
V. V. Zatolokin ◽  
V. M. Shipulin

The introduction of autovenous coronary artery bypass grafting (CABG) marked the era of surgical revascularization in patients with coronary artery disease. It provided effective treatment for angina and significantly improved the long-term prognosis. Venous transplants today remain the most popular conduits in coronary surgery due to their availability, ease of harvesting, and the absence of length restrictions. Despite the advantages of autovenous CABG, the main disadvantage is the high incidence of venous graft failure, which represents an important and unresolved problem in cardiac and cardiovascular surgery. On the other hand, the traditional allocation of a large saphenous vein implies the dissection of soft tissues throughout the length of the isolated conduit. Traumatic dissection causes a long-lasting persistent pain syndrome after surgery, frequent abnormalities in  skin sensitivity, and a high incidence of wound complications in the lower extremities. These complications lengthen the period of rehabilitation of patients and worsen the quality of life. There is an approach of isolating the vein in a block with surrounding tissues to optimize the long-term functioning of the venous shunt, however, this technique is even more traumatic than the traditional method, and therefore its use is limited in practice. On the other hand, the introduction of minimally invasive methods of isolation allowed to reduce the incidence of wound complications and to improve the cosmetic result, but there is no convincing data regarding the effect on the consistency of shunts in the long-term postoperative period. The problems associated with the use of venous conduits in CABG are multifaceted, and their solutions are necessary to improve the effectiveness of surgical revascularization.


1992 ◽  
Vol 262 (3) ◽  
pp. H678-H683 ◽  
Author(s):  
N. Toda ◽  
T. Matsumoto ◽  
K. Yoshida

In monkey coronary artery strips contracted with prostaglandin (PG) F2 alpha or K+, exchange of entire N2 for O2 in the gas aerating the bathing media produced a contraction. Endothelium denudation did not alter the response. Aspirin, indomethacin, and ONO 3708, a PG receptor antagonist, markedly inhibited the hypoxia-induced contraction, whereas superoxide dismutase and OKY 046, a thromboxane (Tx) A2 synthesis inhibitor, were ineffective. Diltiazem depressed the contraction. Hypoxia increased the release of PGE2 but not 6-keto-PGF1 alpha and TxB2. Contractions induced by hypoxia of human coronary artery strips were also independent of the endothelium but were suppressed by indomethacin and diltiazem. On the other hand, dog coronary artery contractions induced by hypoxia were attenuated by endothelium denudation but were not influenced by indomethacin. It may be concluded that the hypoxia-induced contraction of monkey and human epicardial coronary arteries is associated with vasoconstrictor PGs released from subendothelial tissues; however, TxA2 and superoxide anion are not involved. The dog coronary artery contraction appears to be elicited by substance(s), other than cyclooxygenase products, released from the endothelium.


2017 ◽  
Vol 12 (4) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Lenka Tůmová ◽  
Iva Dolečková ◽  
Helena Hendrychová ◽  
Marie Kašparová

The total arbutin content in the leaves of all the studied Bergenia plants ( B. crassifolia, B. ciliata and B. x ornata) was determined. The highest values of the arbutin content have been established for B. crassifolia (58.9 ± 0.7 mg.g−1 DW) and B. x ornata (51.0 ± 1.21 mg.g−1 DW), and the lowest for B. ciliata (5.9 ± 0.6 mg.g−1 DW). Arbutin concentration in the Bergenia leaves was the lowest in spring, in the autumn, on the contrary it increased. All the tested aqueous extracts caused a dose-dependent increase in diphenolase activity of fungal tyrosinase in a similar way as arbutin. On the other hand, all the ethanol extracts inhibited the diphenolase activity of tyrosinase.


1983 ◽  
Vol 61 (11) ◽  
pp. 1409-1417 ◽  
Author(s):  
V. S. R. Krishnamurty ◽  
P. J. Kadowitz

The vascular effects of adenosine triphosphate (ATP) were examined in the isolated perfused mesenteric arteries of the rabbit. Bolus injections of ATP (1 × 10−8 to 10−6 mol) induced a dose-dependent vasoconstrictor response at resting perfusion pressure, while continuous perfusion with ATP briefly elicited a vasoconstrictor response which was not maintained. Perfusion with phentolamine (2.65 × 10−6 M, an α-adrenergic receptor blocker), indomethacin (8.37 × 10−6 M, an inhibitor of cyclooxygenase), atropine (1 × 10−7 M, a muscarinic receptor blocker), and hydralazine (2 × 10−4 M, a vascular smooth muscle inhibitor) for a period of 1 h had no effect on vasoconstrictor responses to ATP. However, pretreatment with reserpine (2 mg∙kg−1∙day−1 for 2 days), an agent which depletes catecholamines, potentiated responses to ATP. On the other hand, when vascular tone was increased with an isoosmotic 60 mM K+ depolarizing Krebs bicarbonate solution, bolus injections of ATP elicited a prominent dose-dependent vasoconstriction followed by a prominent vasodilation. The degree of vasodilation but not of vasoconstriction elicited by ATP was greater in small terminal arteries with branches (<0.5 mm outside diameter (o.d.)) than in the medium size arteries (≤1 mm o.d.) without terminal branches. Both the vasoconstrictor and vasodilator responses were unaffected by a perfusion with atropine, indomethacin, or eicosatetraynoic acid (ETYA, 1 × 10−4 M) for 1 – 2 h. The vasoconstrictor responses were potentiated while the vasodilator responses were inhibited significantly by perfusion with propranolol (3 × 10−6 M) and phentolamine (2.65 × 10−6 M) together for 1 h or by pretreatment with reserpine followed by cold storage at 2 °C for 24 h. Perfusion with 8-phenyltheophylline (4 × 10−6 M (8-PT), an adenosine receptor blocker) for 1 h significantly inhibited by the vasodilator responses to bolus injections of adenosine but not to ATP. Further, ATP but not adenosine elicited a much more prominent vasodilator response on norepinephrine (NE) induced tone than on 60 mM K+. These studies suggest that ATP may induce vasoconstriction independent of activation of α-adrenergic or muscarinic receptors or enhanced synthesis of prostaglandins. This vasoconstriction is resistant to the inhibitory influence of hydralazine. On the other hand, the vasodilator response to ATP may be mediated through its interactions with released or circulating norepinephrine.


2019 ◽  
Vol 34 (1) ◽  
pp. 24-32
Author(s):  
Y. Y. Vecherskiy ◽  
D. V. Manvelyan ◽  
V. V. Zatolokin ◽  
V. M. Shipulin

The introduction of autovenous coronary artery bypass grafting (CABG) marked the era of surgical revascularization in patients with coronary artery disease. It provided effective treatment for angina and significantly improved the long-term prognosis. Venous transplants today remain the most popular conduits in coronary surgery due to their availability, ease of harvesting, and the absence of length restrictions. Despite the advantages of autovenous CABG, the main disadvantage is the high incidence of venous graft failure, which represents an important and unresolved problem in cardiac and cardiovascular surgery. On the other hand, the traditional allocation of a large saphenous vein implies the dissection of soft tissues throughout the length of the isolated conduit. Traumatic dissection causes a long-lasting persistent pain syndrome after surgery, frequent abnormalities in  skin sensitivity, and a high incidence of wound complications in the lower extremities. These complications lengthen the period of rehabilitation of patients and worsen the quality of life. There is an approach of isolating the vein in a block with surrounding tissues to optimize the long-term functioning of the venous shunt, however, this technique is even more traumatic than the traditional method, and therefore its use is limited in practice. On the other hand, the introduction of minimally invasive methods of isolation allowed to reduce the incidence of wound complications and to improve the cosmetic result, but there is no convincing data regarding the effect on the consistency of shunts in the long-term postoperative period. The problems associated with the use of venous conduits in CABG are multifaceted, and their solutions are necessary to improve the effectiveness of surgical revascularization.


1982 ◽  
Vol 2 (11) ◽  
pp. 1299-1303
Author(s):  
S Sora ◽  
M Bianchi

The effect of atenolol, propranolol, trifluoperazine, and caffeine on the occurrence of meiotic diploid and disomic products in Saccharomyces cerevisiae was investigated. We demonstrated that atenolol, propranolol, and trifluoperazine reduce the occurrence of meiotic diploid products and that propranolol also slightly decreases the spontaneous frequency of disomics. On the other hand, caffeine appears to be a powerful inducer of diploid meiotic products, but also shows a lesser effect on disomic induction. Since spontaneous or caffeine-induced diploids arise from a failure of the second meiotic division, it appears that the target of these drugs is at the beginning of the second meiotic division. The only common effect of trifluoperazine and propranolol, mainly investigated in mammals, was an inhibition of calmodulin activity via direct interaction. We tend, therefore, to believe that calmodulin activity must be a crucial point for the second meiotic division to begin. The increased induction of diploids, due to caffeine, may be interpreted as a consequence of an increased cyclic AMP level.


2019 ◽  
Vol 36 (2) ◽  
pp. 211-219 ◽  
Author(s):  
Ryota Sato ◽  
Nobuhiro Ariyoshi ◽  
Daisuke Hasegawa ◽  
Erin Crossey ◽  
Natsumi Hamahata ◽  
...  

Background: Although surviving sepsis campaign guidelines recommend the use of inotropes in the presence of myocardial dysfunction, the effects of inotropes, including epinephrine, dobutamine, and milrinone, on in-hospital mortality in patients with septic shock remains unclear. Materials and Methods: We conducted an international,2-center, retrospective cohort study. The Cox proportional hazards regression model with time-varying covariates was used to investigate whether epinephrine, milrinone, or dobutamine reduces in-hospital mortality in patients with septic shock. Sensitivity analysis was performed using propensity score matching. The primary outcome was in-hospital mortality. The secondary outcome included atrial fibrillation (Afib) with a rapid ventricular response (RVR) in the intensive care unit (ICU) and ICU-free days. Results: A total of 417 patients with septic shock were included, 72 (17.3%) of whom received inotropes. The use of epinephrine and dobutamine was associated with significantly higher in-hospital mortality (epinephrine, hazard ratio [HR]: 4.79, 95% confidence interval [CI]: 2.12-10.82, P = .001; dobutamine, HR: 2.53, 95% CI: 1.30-4.95, P = .046). The effects of epinephrine and dobutamine were time- and dose-dependent. The use of milrinone was not associated with increased mortality (HR: 1.07, 95% CI: 0.42-2.68, P = .345). The use of epinephrine, dobutamine, and milrinone was associated with significantly increased odds of Afib with RVR (epinephrine, odds ratio [OR]: 3.88, 95% CI: 1.11-13.61, P = .034; dobutamine, OR: 3.95, 95% CI: 1.14-13.76; and milrinone, OR: 3.77, 95% CI: 1.05-13.59). On the other hand, the use of epinephrine, dobutamine, and milrinone was not associated with less ICU-free days (epinephrine, adjusted OR: 0.30, 95% CI: 0.09-1.01, P = .053; dobutamine, adjusted OR: 0.91, 95% CI: 0.29-2.84; and milrinone, adjusted OR: 0.60, 95% CI: 0.19-1.87). Conclusion: The present study showed that the use of epinephrine and dobutamine was associated with significantly increased in-hospital mortality in patients with septic shock. These effects were both time- and dose-dependent. On the other hand, the use of milrinone was not associated with increased in-hospital mortality.


1989 ◽  
Vol 9 (2) ◽  
pp. 207-212
Author(s):  
M. D. Fernández-Moreno ◽  
E. Arilla ◽  
J. C. Prieto

The effects of experimental uremia on the concentration of vasoactive intestinal peptide (VIP) in duodenum as well as on the interaction of this neuropeptide with the corresponding epithelial cells were studied in rats. Duodenal VIP concentration was significantly decreased in uremic rats as compared to control animals. The specific binding of VIP to duodenal epithelial cells increased in rats with uremia due to an increase in the number of VIP receptors rather than a change in the binding affinity or in the extent of VIP degradation. On the other hand, the efficacy but not the potency of VIP upon cyclic AMP generation varied in parallel to that observed at the receptor level.


1999 ◽  
Vol 54 (3-4) ◽  
pp. 186-190 ◽  
Author(s):  
Dahabada Helena José Lopes ◽  
José Roberto Meyer-Fernandes ◽  
Mauro Sola-Penna

Trehalose has been described to protect several enzymes against destabilizing conditions. This sugar is naturally accumulated by yeast as a stress protectant. A common stress condition that yeast is normally submitted is the presence of ethanol, the by-product of fermentation process of several yeast. In this paper we show the effects of trehalose and ethanol, alone or together, on yeast pyrophosphatase, and the effects of these compounds on inhibition and unfolding of pyrophosphatase promoted by urea. We show that both trehalose and ethanol inhibit pyrophosphatase in a dose-dependent manner, and that the presence of ethanol does not modify the inhibition promoted by trehalose as well as the presence of trehalose does not modify the inhibition promoted by ethanol. The effects of trehalose on pyrophosphatase are completely reversible, but the inhibition caused by ethanol was only partially reversible. Incubation of pyrophosphatase with 10% (v/v) ethanol promoted an inhibition of 15%, and the control activity was completely recovered after removal of ethanol. On the other hand, when pyrophosphatase was incubated with 20% (v/v) ethanol an inhibition of 40% of the control activity was observed which persisted after removal of ethanol. Ethanol also potentiates the inhibition of pyrophosphatase promoted by urea, and contributes for an irreversible inactivation and unfolding of pyrophosphatase in the presence of urea. Trehalose, that protects this enzyme against the inhibition and unfolding promoted by the chaotropic compound urea, was inefficient to protect against the effects of ethanol. Trehalose was also efficient to prevent an irreversible inactivation induced by urea.


2017 ◽  
Vol 2 (1) ◽  
pp. 5-9
Author(s):  
Cristian Iván García Rincón ◽  
Luz Yaneth Becerra Salazar ◽  
Germán Alberto Moreno Gómez ◽  
Henry Mauricio Arenas Quintero

La exposición a cantidades excesivas de yodo bloquea la actividad de la enzima peroxidasa tiroidea (TPO), un fenómeno conocido como efecto de Wolff-Chaikoff. Clínicamente, éste puede llevar a hipotiroidismo. Por el contrario, cuando un tirocito contiene valores bajos de yodo y es expuesto a elevadas concentraciones del mismo, aumenta de forma significativa la producción de hormona tiroidea, llevando frecuentemente a hipertiroidismo clínico y bioquímico, fenómeno conocido como efecto de Jod-Basedow. Tanto el hiper como el hipotiroidismo aumentan el riesgo de enfermedad arterial coronaria, miopatía ventricular izquierda, anormalidades electrofisiológicas, además de incrementar la mortalidad cardiovascular y por todas las causas.Abstract Exposure to excessive amounts of iodine blocks the activity of the enzyme thyroid peroxidase (TPO), a phenomenon known as Wolf-Chaikoff effect. Clinically, this effect can lead to hypothyroidism. On the other hand, when thyrocites have low iodine levels and are exposed to a high iodine concentration, they increase significantly their production of thyroid hormone thus leading to hyperthyroidism, a phenomenon known as Jod-Basedow effect. Both hypothyroidism and hyperthyroidism increase the risk of coronary artery disease, left cardiomyopathy, electrophysiological abnormalities, and all-cause mortality.


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