The effects of 3,4‐dihydro‐8‐(2‐hydroxy‐3‐isopropylaminopropoxy)‐3‐nitroxy‐2H‐1‐benzopyr an (K‐351) and its denitrated derivative on smooth muscle cells of the dog coronary artery

Kou, Katsuhiro; Suzuki, Hiroyoshi

doi:10.1111/j.1476-5381.1983.tb10523.x

Cited by 31 publications

(17 citation statements)

References 12 publications

(10 reference statements)

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“…Kou & Suzuki (1983) showed that both nipradilol and nitroglycerin induced vasorelaxation without any electrophysiological changes of the sarcolemmal membrane in canine coronary artery. It is reported that nitroglycerin-induced relaxation is to some extent related to an inhibition of Ca2" influx, but is mainly due to increased extrusion of Ca2" (Ito & Kuriyama, 1983).…”

Section: Discussionmentioning

confidence: 94%

“…It was synthesized with the aim of allowing the compound to possess both the actions of /3-adrenoceptor antagonist and a nitrate (Uchida et al, 1983). The direct relaxant action of nipradilol on vascular smooth muscle has been demonstrated in isolated arteries and vein (Uchida 1983; Kou & Suzuki, 1983;Sakanashi et al, 1984). Since a nitroxy group is present within the nipradilol molecule, a portion of its dilator effect may share some characteristics with other nitroxy group-containing vasodilators (Uchida et al, 1983;Kou & Suzuki, 1983;Sakanashi et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

“…The direct relaxant action of nipradilol on vascular smooth muscle has been demonstrated in isolated arteries and vein (Uchida 1983; Kou & Suzuki, 1983;Sakanashi et al, 1984). Since a nitroxy group is present within the nipradilol molecule, a portion of its dilator effect may share some characteristics with other nitroxy group-containing vasodilators (Uchida et al, 1983;Kou & Suzuki, 1983;Sakanashi et al, 1984). Nipradilol increases guanosine 3':5'-cyclic monophosphate (cyclic GMP) production and relaxes smooth muscle (Sugiyama 1988;Imai et al, 1990;Nakazawa et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

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Some effects of nipradilol, a β‐antagonist possessing a nitroxy group, on smooth muscle of the pig coronary artery

Abe

Nakamura

Kobayashi

1996

British J Pharmacology

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1 The effects of nipradilol, a ,B-adrenoceptor antagonist which possesses a nitroxy group, on cytosolic Ca2+ concentration ([Ca2+i) and on tension development were simultaneously measured by front-surface fluorometry and fura-2-loaded strips in the proximal portion of pig coronary arteries.2 Nipradilol reduced in a concentration-dependent manner both the [Ca2+]i and tension, irrespective of whether the strips were unstimulated or exposed to either high K+ or histamine containing solutions. However, both in the case of contractions induced by high K+-depolarization and histamine stimulation, for a given [Ca2+]i elevation the tension which developed in the presence of nipradilol was smaller than that generated in its absence, so that the [Ca2 +]i-tension curves during the contraction were shifted to the right.3 In the absence of extracellular Ca2 , the [Ca2i], elevation due to the release of Ca2+ from histaminesensitive store was inhibited by nipradilol. Nipradilol had no effect on the [Ca2+]i elevation due to the release of Ca2+ from caffeine-sensitive stores; however, it did inhibit the caffeine-induced increase in tension. A derivative of nipradilol, which lacked a nitroxy molecule (Nip(-N)), had no effect on the At lower concentrations, nipradilol acted as a fl-blocker, the IC50 value being smaller than that of Nip(-N), and at higher concentrations, it acted as a nitrovasodilator. 5 Thus, it is suggested that, at lower concentrations, nipradilol, an antianginal drug, acts as a ,Badrenoceptor antagonist. At higher concentrations, it relaxes the proximal portion of the coronary artery by directly reducing [Ca2']i and the Ca2+-sensitivity of the myofilaments, apparently due to the presence of the nitroxy molecule.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Some effects of nipradilol, a β‐antagonist possessing a nitroxy group, on smooth muscle of the pig coronary artery

Abe

Nakamura

Kobayashi

1996

British J Pharmacology

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“…In both moderately ischemic areas and severely ischemic areas (MBF 0-20), nipradilol did not affect MBF. One of the reasons why the MBF in the ischemic areas did not decrease in spite of a decrease in myocardial oxygen consumption by nipradilol is considered to be that nipradilol dilates the collateral blood vessels through its nitroglycerin-like vaso dilating action (1,2,14). An increase in blood flow following the dilation of collateral vessels may compensate for a decrease in blood flow in ischemic areas accompanying a decrease in myocardial oxygen con sumption.…”

Section: Discussionmentioning

confidence: 99%

Beneficial effect of nipradilol (K-351) on acute myocardial ischemia. Study of the relationship between regional myocardial blood flow and energy metabolism.

et al. 1990

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Abstract-To examine the effects of nipradilol on ischemic myocardium, experi ments were performed on regional myocardial blood flow (MBF) and energy metabolism in anesthetized, open-chest dogs. Nipradilol at a dose of 0.3 mg/kg was i.v.-administered 10 min after coronary ligation. M BFs at various sites, including ischemic and non-ischemic areas, were determined by the hydrogen gas clearance method. The levels of ATP and creatine phosphate (CP) at the site of MBF deter mination were measured 60 min after ligation, and mitochondrial function (RCI, Q02) in the ischemic and non-ischemic areas was determined. Following nipradilol administration, aortic pressure and heart rate were significantly lowered. In ischemic areas with MBF below 40 ml/min/100 g, nipradilol had no influence on MBF. However, the tissue level of ATP in nipradilol treated hearts was significantly higher as compared with untreated hearts. In the area of mild ischemia with MBF of 40-60 ml/min/100 g, nipradilol preserved the tissue ATP and CP levels in spite of a decrease in MBF. Moreover, an inhibition of the decrease in mitochondrial respiratory function was observed in ischemic areas with MBF below 20 ml/min/ 100 g. Thus, nipradilol administered following ischemia preserved ATP content and mitochondrial function in the ischemic myocardium with reduction of heart rate and aortic pressure. This suggests that nipradilol exerts a cardioprotective effect in acute ischemia. It seems that the cardioprotective effect is due to a decrease in myocardial oxygen demand and preservation of mitochondrial function.

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“…It has been shown that the vasodilating properties are probably due to a-adrenoceptor blocking action, especially a1-blocking action (2)(3)(4), and nitroglycerin like action (5,6). In spontaneously hyper tensive rats, nipradilol produces a long lasting antihypertensive effect (7).…”

mentioning

confidence: 99%

Effects of Nipradilol, a New β-Adrenoceptor Blocking Agent with Vasodilating Properties, on Transmural Energy Metabolism in the Underperfused Canine Heart

Higuchi

Asakawa

1987

Japanese Journal of Pharmacology

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Abstract-Effects of nipradilol on hemodynamics and transmural energy me tabolism of underperfused (ischemic) canine hearts were investigated. The ischemic heart was prepared by constricting a tube connecting the circumflex coronary artery with the carotid artery for 10 min so that the perfusion pressure (CPP) was reduced to 30 mmHg. The reduction in CPP resulted in decreases in coronary blood flow (CBF) by 70%, regional myocardial contractile force (MCF) by 30%, myocardial ATP contents by 32% (inner layer)-22% (outer) and creatine phosphate by 75% (inner)-60% (outer). Increases in the left ventricular end diastolic pressure (LVEDP) by 4.8 mmHg, myocardial inorganic phosphate con tents by 1.9 times (inner)-1 .3 (outer) and lactate by 4.3 times (inner)-2.4 (outer) were also observed. In dogs with normal hearts, an infusion of nipradilol (10 ,ug/ kg/min, i.v., for 1 5 min) decreased CPP by 25%, CBF by 40%, cardiac effort index by 45% and MCF by 30 to 40%, and it slightly increased LVEDP without affecting myocardial high-energy phosphate and lactate levels. In ischemic hearts, nipradilo! infusion starting 5 min before ischemia attenuated the ischemia-induced elevation of LVEDP to 1.8 mmHg, and the ischemia-induced changes in high energy phosphate contents to 1/2 (inner)-1/3 (outer) and changes in lactate to 1 /6 (inner)-1/10 (outer). These results indicate that nipradilol improves the ischemic derangement of both transmural energy metabolism and hemodynamics.

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The effects of 3,4‐dihydro‐8‐(2‐hydroxy‐3‐isopropylaminopropoxy)‐3‐nitroxy‐2H‐1‐benzopyr an (K‐351) and its denitrated derivative on smooth muscle cells of the dog coronary artery

Cited by 31 publications

References 12 publications

Some effects of nipradilol, a β‐antagonist possessing a nitroxy group, on smooth muscle of the pig coronary artery

Some effects of nipradilol, a β‐antagonist possessing a nitroxy group, on smooth muscle of the pig coronary artery

Beneficial effect of nipradilol (K-351) on acute myocardial ischemia. Study of the relationship between regional myocardial blood flow and energy metabolism.

Effects of Nipradilol, a New β-Adrenoceptor Blocking Agent with Vasodilating Properties, on Transmural Energy Metabolism in the Underperfused Canine Heart

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