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Biomedical subjects

S Sunano

Publications and source records attributed to S Sunano.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effects of cyclopiazonic acid and thapsigargin on electromechanical activities and intracellular Ca2+ in smooth muscle of carotid artery of hypertensive rats.

1. The effects of cyclopiazonic acid (CPA) and thapsigargin (TG), both of which are known to inhibit sarcoplasmic reticular Ca(2+)-ATPase, on the mechanical activities, intracellular Ca2+ level and electrical activities of smooth muscle of the carotid artery of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY) were compared. 2. Both CPA and TG induced elevation of tension of the smooth muscle, which was composed of a phasic and a tonic component. The level of tension attained, especially the tonic component, was greater in the preparation from SHRSP. 3. The elevation of tension was associated with an increased intracellular Ca2+ level. Both the elevation of tension and the increase in intracellular Ca2+ were diminished by the removal of extracellular Ca2+ or by the application of verapamil. 4. The resting membrane potential of the preparations from SHRSP were depolarized to a greater extent than those from WKY.CPA depolarized the smooth muscle from both SHRSP and WKY, and the final level was also more depolarized in the preparation from SHRSP. 5. These results indicate that the elevation of tension induced by these drugs is mainly due to increased Ca2+ influx through voltage-dependent Ca2+ channels, and the difference in the action between the preparation from SHRSP and that from WKY can be explained mainly by the changes in the channels. 6. Thus, differences in the action of these drugs on the tension of smooth muscle between preparations from WKY and SHRSP can mainly be explained by the difference in the membrane potential which is related to the difference in voltage-dependent Ca2+ influx.

Animals↗
PubMed1996

Blood pressure and age-dependent changes of endothelium-dependent tension oscillations in different strains of spontaneously hypertensive rats.

The influence of blood pressure and age of spontaneously hypertensive rats on endothelium-dependent tension oscillation of aortic preparation were studied. Rats with different blood pressures, normotensive Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP) and malignant type of SHRSP (M-SHRSP), were used. The effects of antihypertensive treatment of SHRSP on the tension oscillation were also studied. High doses of noradrenaline induced tension oscillations in endothelium-intact preparations of all strains of young rats. The rate of the occurrence of the tension oscillation decreased age-dependently. The decrease was faster when the blood pressure of the rats was higher. Application of acetylcholine in the presence of noradrenaline induced a relaxation and tension oscillations, both of which were negatively dependent on age and blood pressure. Antihypertensive treatment of hypertensive rats with hydralazine or captopril prevented a decrease in incidence of the tension oscillation. These influences of age and blood pressure as well as antihypertensive treatments on the tension oscillation resembled those on the endothelium-dependent relaxation and are thought to be brought about by functional changes of the endothelium.

Acetylcholine↗
PubMed1996

Attenuation of intrinsic active tone by endothelium-derived nitric oxide in aortae of spontaneously hypertensive rats with different levels of blood pressure.

The influences of endothelium on the basal tone of aortae from various strains of spontaneously hypertensive rats with different blood pressure (SHR, SHRSP, M-SHRSP) were studied. Endothelium-intact preparations of aortae from spontaneously hypertensive rats exhibited spontaneous active tone, which was greater in the order of SHR < SHRSP < M-SHRSP. The active tone of the M-SHRSP preparations was about 40% of high-K(+)-induced contraction, while that of normotensive WKY was less than 5%. The active tone was enhanced by the removal of endothelium. The active tone was sensitive to extracellular Ca2+ and abolished by verapamil. The application of N(G)-monomethyl-L-arginine caused the increase in the active tone which was counteracted by L-arginine. These results indicate that the active tone of smooth muscle increases as the blood pressure of the rat increases, and that endothelium attenuates the active tone by releasing nitric oxide (NO) spontaneously. It was also demonstrated that the attenuating action of endothelium was impaired depending on the blood pressure level.

Animals↗
PubMed1995

Alteration in the release of endothelium-derived relaxing factors by alpha-adrenoceptor stimulation in the aorta of stroke-prone spontaneously hypertensive rats.

1. Endothelium-dependent relaxation by alpha-adrenoceptor agonists was examined in the thoracic aorta from normotensive Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP). 2. In ring preparations from both strains, noradrenaline-induced contraction was increased by L-nitro arginine (L-NNA), a NO synthesis inhibitor. 3. L-NNA increased the contraction induced by phenylephrine, an alpha1-adrenoceptor agonist. UK-14304 and clonidine, alpha2-adrenoceptor agonists, did not contract the preparations with intact endothelium. However, these agents contracted preparations when NO synthesis was inhibited. 4. In a precontracted preparation, clonidine and UK-14304 induced relaxations. The relaxations in SHRSP aorta were smaller than those in WKY aorta. 5. These results indicate that alpha-agonists release NO from endothelium in WKY and SHRSP aorta. The mechanism related to NO release by alpha2-adrenoceptor agonist is impaired in SHRSP aorta.

Adrenergic alpha-Agonists↗
PubMed1995

Effects of chronic treatment with carvedilol on abnormalities of endothelium-dependent relaxation and structure of endothelium in resistance arteries of SHRSP.

1. This study investigated the effects of chronic treatment with carvedilol, a beta-blocking agent with an alpha-blocking activity, on blood pressure, endothelium-dependent relaxation and the endothelial structure of the mesenteric resistance artery in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Chronic treatment with carvedilol at a dose range of 30-120 mg/kg per day lowered systolic blood pressure of SHRSP from 234.9 +/- 3.3 to 198.7 +/- 3.1 mmHg at 16 weeks of age. 3. Acetylcholine-induced endothelium-dependent relaxation was impaired in the mesenteric artery from SHRSP and high concentrations of acetylcholine produced contractions. The impairment of the relaxation was abolished in the presence of indomethacin. Carvedilol treatment improved the impairment in the preparation from SHRSP. The structural abnormality of endothelium was observed in the preparation from SHRSP. The abnormality could be prevented by the antihypertensive treatment. 4. These results suggest that the impairment of endothelium-dependent relaxation in the preparation from SHRSP is due to the corelease of an endothelium-derived contracting factor which is considered to be a product of cyclo-oxygenase pathway of arachidonic acid cascade and that the impairment can be prevented by the antihypertensive treatment with carvedilol.

Acetylcholine↗
PubMed1995

Effects of NG-nitro-L-arginine on alpha-agonists-induced contraction of aortae from Wistar Kyoto rats and stroke-prone spontaneously hypertensive rats.

Differences in the influences of endothelium-derived nitric oxside (NO) on alpha-agonists-induced contraction in the aortae of spontaneously hypertensive and normotensive rats were studied by blocking NO synthesis with NG-nitro-L-arginine (L-NNA). L-NNA potentiated the contraction induced by noradrenaline. The potentiation was smaller in the preparation from stroke-prone spontaneously hypertensive rats (SHRSP) than in the preparation from Wistar Kyoto rats (WKY). Similar potentiation was observed in the contraction induced by phenylephrine; the potentiation was also smaller in the preparation from SHRSP. alpha 2-agonists, clonidine and UK-14304 induced dose-dependent contraction only in the presence of L-NNA. The dose-response curves for alpha 2-agonists in SHRSP aorta were different from those in WKY aorta; the maximum tension was observed at the concentration of 10(-6) M in the preparation from WKY, while the contraction further increased up to 10(-4) M in the preparation from WKY. Noradrenaline, clonidine and UK-14304 but not phenylephrine induced relaxation which was blocked by L-NNA. The relaxation was impaired in the preparation from SHRSP in greater extent than that by acetylcholine. It is suggested that basic or noradrenaline-stimulated NO release from endothelium decreased in the preparation from SHRSP and that alpha 2-adrenoceptor of both the endothelium and smooth muscle may be altered in the preparation from SHRSP.

Adrenergic alpha-Agonists↗
PubMed1994

Comparison of endothelium-dependent and -independent tension oscillation in aortae of stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats.

Differences in noradrenaline-induced tension oscillations between aortae from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive control Wistar Kyoto rats (WKY) were studied. Endothelium-intact and -removed ring preparations were made from thoracic aorta of SHRSP and WKY, and isometric contraction was observed. Endothelium-intact preparations from WKY showed tension oscillations in response to high concentration of noradrenaline at significantly higher ratio, while only a few endothelium-removed preparation showed tension oscillations in response to low concentration of the drug. Fifteen out of 41 endothelium-removed preparations from SHRSP showed tension oscillations in response to low concentration of noradrenaline but no preparation showed oscillations in response to high concentration of the drug. Seven and 14 out of 42 endothelium-intact preparations from SHRSP showed oscillatory response to low and high concentration of the drug, respectively. Acetylcholine-induced relaxation and tension oscillations, both of which being significantly less in the preparation from SHRSP. Both the endothelium-independent tension oscillations and endothelium-dependent tension oscillations were abolished by removal of extracellular Ca or by verapamil. It is suggested that aortic smooth muscle of SHRSP possesses the property which produced tension oscillations, while the tension oscillations of WKY aorta is endothelium-dependent. The opening of voltage-dependent Ca++ channel of smooth muscle cell membrane which generates rhythmic contraction is increased in the aorta of SHRSP, while the release of endothelium-derived factors which induces rhythmic activities of smooth muscle cell is decreased.

Animals↗
PubMed1993

Involvement of alpha-adrenoceptors in the endothelium-dependent depression of noradrenaline-induced contraction in rat aorta.

The involvement of endothelium-derived nitric oxide (NO) in the depressant action of the endothelium on noradrenaline-induced contractions and characterization of the receptor involved in the release of NO were studied using rat aorta. The noradrenaline-induced contraction was significantly potentiated by endothelium removal and in the presence of NG-nitro-L-arginine (L-NNA) or NG-monomethyl-L-arginine (L-NMMA). The contraction induced by phenylephrine was also potentiated in the presence of L-NNA. Clonidine could induce contraction only in endothelium-denuded preparations or in the presence of L-NNA. The potentiating action of L-NNA on noradrenaline-induced contractions could also be observed in the presence of yohimbine or rauwolscine, although dose-response curves were shifted to the right. The depression of noradrenaline-induced contractions observed in the presence of the endothelium was increased by repeated stimulation. The depression was prevented by L-NNA and this effect was reversed by L-arginine. These results indicate the possibility that NO can be released through stimulation of alpha 1- and alpha 2-adrenoceptors on the endothelium and depresses noradrenaline-induced contractions of smooth muscle, although the contribution of the respective adrenoceptors remains to be investigated. The release of NO was increased when the stimulation was applied repeatedly.

Animals↗
PubMed1993

Effects of NG-nitro-L-arginine on electrical and mechanical responses to stimulation of non-adrenergic, non-cholinergic inhibitory nerves in circular muscle of the rat gastric fundus.

The effects of L-nitroarginine (L-NNA), an inhibitor of nitric oxide (NO) synthesis, on non-adrenergic, non-cholinergic inhibitory transmission in the circular smooth muscle of the rat gastric fundus were studied. The relaxation in response to nerve stimulation in the presence of guanethidine and atropine was depressed by the application of L-NNA (10(-4) M), and the depression was reversed by the addition of L-arginine (10(-4) M). The time course of the relaxation was altered from a monophasic to biphasic one, both of which were depressed. Stimulation of non-adrenergic, non-cholinergic nerves initiated inhibitory junctional potentials (i.j.p.). In addition, slow after-hyperpolarization was observed when stimuli were applied repeatedly at frequencies higher than 0.5 Hz. L-NNA reduced the i.j.p. partially and abolished the after-hyperpolarization, indicating the partial involvement of NO in non-adrenergic, non-cholinergic inhibitory transmission. The effects of L-NNA on the nerve-mediated relaxation are thought to be due to changes in the i.j.p. and slow after-hyperpolarization.

Animals↗
PubMed1993

[Elevation of spontaneous tone and effects of antihypertensive treatments in arterial smooth muscle of spontaneously hypertensive rats].

Mechanisms of elevation of active tone in arterial smooth muscle of spontaneously hypertensive rats and effects of antihypertensive treatments are reviewed. Spontaneously hypertensive rats are created by Okamoto et al. and classified mainly into three strains, SHR, SHRSP and M-SHRSP. Blood pressure of the rats is higher in this order. The aortic smooth muscle of these rats exhibits elevation of the active tension (tone) under non-stimulated condition. The active tone is greater as the blood pressure of the rats elevated and good correlation between blood pressure and active tone can be obtained. The active tone is sensitive to extracellular Ca and abolished by the removal of extracellular Ca or by the application of Ca-antagonists. It is also associated with increased intracellular Ca level. These results indicate that the active tone is brought about by increase in voltage-dependent Ca channel opening of the cell membrane. Increased voltage-dependent Ca channel opening, i.e. membrane depolarization and increased inward Ca current can be a cause of the elevated tone. Abnormalities in the cellular mechanisms for relaxation of the smooth muscle can also contribute to the elevation of the active tone. Endothelium suppresses the active tone, probably releasing endothelium-derived relaxing factor or hyperpolarizing factor. The suppression of contraction by endothelium is impaired in the blood vessels of spontaneously hypertensive rats, depending on the degree of hypertension. Antihypertensive treatments prevent the development or elevation of the active tone. It also prevents the impairment of function of endothelium. Thus, the maintained hypertension alters functions of smooth muscle membrane and endothelium. The degree and duration of hypertension are thought to be determinant factors of these abnormalities.

Animals↗
PubMed1993

Relationship between blood pressure and smooth muscle tone in aortae of hypertensive rats: roles of [Ca2+].

Spontaneously developed tension (active tone) and intracellular Ca2+ level of aortae from spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP), malignant SHRSP (M-SHRSP) and control Wistar Kyoto rats (WKY) were compared. Systolic blood pressure of WKY, SHR, SHRSP and M-SHRSP was 130 mmHg, 200 mmHg, 250 mmHg and 260 mmHg, respectively. Preparations from all strains of spontaneously hypertensive rats exhibited active tone which was abolished by the removal of extracellular Ca2+ or by the application of verapamil. The active tone was greater in the order of aortae from SHR < SHRSP < M-SHRSP. Intracellular Ca2+ level measured by Fura-2 method decreased by the removal of extracellular Ca2+. The degree of the decrease was greater as the blood pressure of the rats increased, indicating the greater elevation of intracellular Ca2+ level in the pressure of extracellular Ca2+. A correlation was obtained between the active tone, intracellular Ca2+ level and blood pressure. Thus, it was demonstrated that the development of the active tone is brought about by the changes in Ca2+ influx of smooth muscle cell membrane and the degree of the change is positively related to the degree of hypertension.

Animals↗
PubMed1992

Effects of chronic treatment with SQ29852 on spontaneous smooth muscle tone and endothelium-dependent relaxation in aorta of stroke-prone spontaneously hypertensive rats.

The effects of chronic treatment with SQ29852, an angiotensin-converting enzyme inhibitor, on spontaneous smooth muscle tone and endothelium-dependent relaxation of aorta from stroke-prone spontaneously hypertensive rats (SHRSP) were studied and compared with those of captopril. Endothelium-removed aorta from 16-week-old SHRSP exhibited a high amplitude of spontaneously developed active tension (active tone), whereas no active tone was observed in the preparation from control normotensive Wistar-Kyoto (WKY) rats. Treatment with SQ29852 or captopril at age 5-16 weeks prevented the development of hypertension. No active tone could be detected in the preparation from SQ29852-treated SHRSP. Endothelium-dependent relaxation was markedly reduced in the preparation from nontreated SHRSP compared with WKY rats. Treatment with SQ29852 prevented the impairment of endothelium-dependent relaxation. It was also shown that norepinephrine-induced contraction was markedly depressed in endothelium-intact aorta from SQ29852-treated rats. The effects of SQ29852 were more prominent than those of hydralazine when blood pressure was maintained at similar levels. It was suggested that SQ29852 exerts an action on both vascular smooth muscle and endothelium that is mediated by the inhibition of angiotension-converting enzyme in addition to indirect actions of SQ29852 that are brought about by blood pressure lowering.

Acetylcholine↗
PubMed1992

Potentiation of twitch contraction in guinea pig ureter by sodium vanadate.

The effect of sodium vanadate on action potential and twitch contraction of guinea pig ureter was studied and compared with that of ouabain, elevated K+, low temperature, and a Ca agonist (BAY K 8644), which can be expected to exert certain comparative effects. Sodium vanadate markedly potentiated twitch contraction. Potentiation by vanadate was associated with marked prolongation of relaxation time. Sodium vanadate caused only slight depolarization of the membrane but marked changes in action potential. The duration of action potential was prolonged and the number of oscillatory spike potentials increased. These effects were different from those of other treatments. It is concluded that prolongation of action potential and the increase in the number of spikes are the main cause of potentiation of twitch contraction by sodium vanadate. In addition, inhibition of Ca pump activity of the smooth muscle membrane system by vanadate might also be involved in potentiation of twitch contraction.

Action Potentials↗
PubMed1991

The relaxation and Ca-pump inhibition in mesenteric artery of normotensive and stroke-prone spontaneously hypertensive rats.

The influences of low temperature and vanadate, both of which have been known to inhibit the Ca-pump activity of membranous systems of smooth muscle cells, on the relaxation of mesenteric artery of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) were studied. Relaxation was induced by the removal of extracellular Ca in high-K-depolarized preparations, so that the involvement of receptor kinetics and changes in membrane potential could be excluded. Relaxation was significantly slower in the preparation from SHRSP than in that from SHRSP. Low temperature prolonged relaxation in preparations from both SHRSP and WKY. No difference in the effect of low temperature was observed between the preparations, which showed Q10 values between 2.8 and 3.5 for 50 and 80% relaxation time. Sodium vanadate also prolonged the time course of relaxation in both preparations. No difference in the effect of sodium vanadate was observed between the preparations from WKY and SHRSP. These results suggest that Ca-pump activity is involved in the relaxation of K-depolarized smooth muscle of mesenteric arteries from both WKY and SHRSP. However, the difference in the pump activity may not contribute greatly to the difference in the relaxation of K-depolarized preparations by the removal of extracellular Ca.

Animals↗