Miyoko Tsukada

Comparison of vasoconstrictor actions of norepinephrine and potassium chloride before and after damage of endothelium by saponin

SummaryUsing isolated and perfused mesenteric arterial preparations of dogs, vasoconstrictor responses to intraluminal norepinephrine and potassium chloride were investigated in the presence and absence of the endothelium. Intraluminal administration of saponin readily removed the endothelium. Saponin (1–3 mg) caused an increase in perfusion pressure, and then approximately 20 min later perfusion pressure became stable at a somewhat higher level than that of the control. A larger dose of saponin (10 mg) caused a tremendous but temporary increase of perfusion pressure. KCl-induced vasoconstriction was significantly enhanced by pretreatment with 0.3, 1, and 3 mg saponin, but norepinephrine-induced constriction was not modified significantly. Moreover, it was demonstrated that diltiazem, a potent Ca antagonist, inhibited the KCl-induced vasoconstriction more readily in the absence than in the presence of the endothelium.

POSSIBLE INVOLVEMENT OF MUSCARINIC M1 AND M3 RECEPTOR SUBTYPES MEDIATING VASODILATION IN ISOLATED, PERFUSED CANINE LINGUAL ARTERIES

1. Using the cannula insertion method, muscarinic receptor subtypes were analysed in isolated, perfused canine lingual arteries preconstricted with phenylephrine.

Histamine-induced vasodilations mediated by H1- and H2-receptors in isolated rat common carotid arteries

SummaryUsing the cannula inserting method, the vasodilatory effects of histamine were analysed employing selective histamine H1- and H2-receptor agonists and antagonists in isolated, perfused rat common carotid arterial preparations which were preconstricted by a continuous infusion of phenylephrine with propranolol. Histamine, 2-pyridylethylamine (2-PEA) (a selective H1-agonist) and dimaprit (a selective H2-agonist) produced a vasodilation in a dose-related manner. The order of potency was histamine > dimaprit > 2-PEA. Histamine-induced dilations were significantly inhibited by either diphenhydramine (a selective H1-antagonist) or cimetidine (a selective H2-antagonist). 2-PEA-induced dilations were significantly inhibited by diphenhydramine but not by cimetidine. Dimaprit-induced dilations were significantly blocked by cimetidine but not by diphenhydramine. ACh-, histamine-, 2-PEA- and dimaprit-induced dilations were significantly suppressed by removal of the endothelium. From these results, it is concluded that (1) isolated rat common carotid arteries have both H1-and H2-receptors, (2) there are few vasoconstrictory H1-receptors, (3) both H1- and H2-receptors mediate only vasodilation but not vasoconstriction, and (4) EDRF from the endothelium might participate in histamine-induced vasodilation via not only H1- but also H2-receptors.

Genetic control of responsiveness of rat liver supernatant aldehyde dehydrogenase to phenobarbital and 3-methylcholanthrene

The responsiveness of the hepatic supernatant NAD+-dependent aldehyde dehydrogenase with a high Km value (high Km-AldDH) to phenobarbital (PB) and 3-methylcholanthrene (3-MC) treatment was studied in male rats of three strains; Wistar, Long-Evans, and Sprague-Dawley.A remarkable strain difference in the response of the enzyme to PB or 3-MC was observed. In rats of the Wistar strain the enzyme activity remained unchanged (“non-responsive”) in all rats after treatment with PB while it increased (“responsive”) 5- to 19-fold in all rats after treatment with 3-MC. The enzyme activity increased 8- to 20-fold and 2- to 8-fold respectively after treatment with PB and 3-MC in all rats of the Long-Evans strain. In rats of the Sprague-Dawley strain the enzyme activity remained unchanged in half of all the rats treated with PB or 3-MC and increased 2- to 7-fold over the basal level in half of the treated rats. The non-responsive rats to PB were all responsive to 3-MC treatment while the responsive rats to PB were responsive in 65% and non-responsive in 35% to 3-MC treatment.

Acetaldehyde level in the blood and liver aldehyde dehydrogenase activities in trichloroethylene-treated rats.

The liver NAD+-dependent aldehyde dehydrogenase (AldDH) activity and the acetaldehyde level in the blood during ethanol metabolism after trichloroethylene (trichlene) exposure were studied in rats. Trichlene inhalation caused large elevations in acetaldehyde levels during ethanol metabolism and caused decreases in the activity of the AldDH with a low Km value in mitochondrial and soluble fractions of liver cells. No significant effects were found in the activity of the high Km-enzyme in mitochondrial, soluble and microsomal fractions. Time course of inhibition of the mitochondrial low Km-enzyme and that of elevations in acetaldehyde levels during ethanol metabolism after trichlene exposure were similar. These findings suggest that acetaldehyde formed from ethanol in vivo is oxidized primarily by the mitochondrial low Km-enzyme.

Evidence for the existence of postsynaptic beta-1 and beta-2 adrenoceptors in isolated simian facial veins

SummaryWith the use of a steel cannula inserting method, the actions of the beta-adrenoceptor agonists, noradrenaline (NA, a mixed agonist), isoprenaline (a mixed agonist), dobutamine (a selective beta-1 agonist), salbutamol, and procaterol (selective beta-2 agonists), were investigated on isolated and perfused simian facial veins. Each beta-agonist usually induced a vasodilation in a dose-related manner in non-preconstricted vessel preparations. The rank order of potency was isoprenaline ≫ NA > dobutamine > salbutamol > procaterol. NA- and isoprenaline-induced vasodilations were inhibited by either metoprolol (a selective beta-1 adrenoceptor antagonist) or ICI 118,551 (a selective beta-2 antagonist). After beta-1 blockade, NA produced a vasoconstriction which was readily blocked by bunazosin (an alpha-1 antagonist). Dobutamine-induced vasodilations were strongly suppressed by metoprolol and slightly blocked by ICI 118,551. Salbutamol-induced vasodilations were blocked by metoprolol, while ICI 118,551 more markedly inhibited these dilations. From these results, it was concluded that there are abundant beta-adrenoceptors and predominantly beta-1 adrenoceptors in isolated simian facial veins.

Effect of temperature on responses of dog isolated lingual and mesenteric arteries to vasoactive substances.

1. The effects of temperature on submaximal vasoconstriction to an intraluminal administration of noradrenaline (NA), phenylephrine, tyramine and KCl were investigated in canine isolated and perfused lingual and mesenteric arteries, using the cannula‐inserting method.

BRADYKININ-INDUCED VASCULAR RESPONSES IN DOG ISOLATED LINGUAL ARTERY

1. Kinin‐induced vascular responses were studied and kinin receptor subtypes were characterized in canine isolated and preconstricted lingual arteries.

Blocking effects of nipradilol on vasoconstrictor responses to periarterial nerve stimulation and α-adrenoceptor agonists in isolated and perfused canine mesenteric arteries

The stainless steel cannula inserting method was used to observe effects of nipradilol and prazosin on responses to periarterial electrical nerve stimulation and intraluminal administration of noradrenaline or phenylephrine in isolated and perfused canine mesenteric arteries. With small doses, nipradilol slightly potentiated vasoconstrictor responses to noradrenaline, but not periarterial stimulation. With a relatively large dose, nipradilol almost uniformly suppressed both periarterial stimulation-induced and noradrenaline- or phenylephrine-induced vasoconstriction. On the other hand, prazosin inhibited noradrenaline-induced vasoconstriction at small doses but not periarterial nerve stimulation-induced vasoconstrictions. At any doses, prazosin strongly inhibited noradrenaline-induced constrictions more markedly than periarterial stimulation-induced constrictions. It is concluded that nipradilol has a dominant inhibitory property on periarterial nerve stimulation-induced constriction in isolated canine mesenteric arteries.

Effect of chronic administration of acetaldehyde by inhalation on (Na+ + K+)-activated adenosine triphosphatase activity of rat brain membranes

The effect of chronic acetaldehyde inhalation on (Na+ + K+)-ATPase (EC 3.6.1.3) activities of subcellular fractions of the rat cerebral cortex was studied. Chronic administration of acetaldehyde by inhalation for 4-21 weeks caused significant increases in the enzyme activities of both the synaptosomal plasma membrane (SPM) fraction and the microsomal (MC) fraction. This indicates the change in neural membrane functions of the brain after acetaldehyde treatment. Mg2+-ATPase activities of both subcellular fractions remained unchanged after acetaldehyde treatment.