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T Hano

Publications and source records attributed to T Hano.

At least 55 records · Page 3Linked to original sources
PubMed1994

Angiotensin II subtype 1 receptor modulates epinephrine release from isolated rat adrenal gland.

To elucidate the role of subtypes of the angiotensin (AT) II receptor in epinephrine release from the adrenal gland, the effects of AT II subtype 1 (AT1) receptor and AT II subtype 2 (AT2) receptor antagonists on AT II-induced modulation of epinephrine release were examined. Seven-week-old Wistar rats were used in this study. The left adrenal gland was perfused in a retrograde fashion. The effects of AT II on basal epinephrine release and epinephrine release by electrical stimulation were examined before and after treatment with CV-11974 (CV), an AT1 receptor antagonist, or PD123319 (PD), an AT2 receptor antagonist. AT II increased epinephrine release from the adrenal gland. CV almost completely suppressed AT II-induced increases in epinephrine release. In contrast, PD had no significant effects on AT II-induced increases in epinephrine release. These results suggest that AT II increases epinephrine release from the adrenal medulla via the AT1 receptor.

Adrenal Glands↗
PubMed1993

Production of nerve growth factor by cultured vascular smooth muscle cells from spontaneously hypertensive and Wistar-Kyoto rats.

OBJECTIVE: Nerve growth factor (NGF) is a neurotrophic protein which acts on peripheral sympathetic nerves. Elevated NGF in vascular tissues of young spontaneously hypertensive rats (SHR) has been reported. The aim of the present study was to compare the amount of NGF secreted from cultured vascular smooth muscle cells (VSMC) and mesenteric artery and thoracic aorta segments from SHR and Wistar-Kyoto (WKY) rats. METHODS: VSMC prepared by the enzyme digestion method from the thoracic aortic media of 14-week-old SHR and age-matched WKY rats were subcultured in Dulbecco's modified Eagle's medium containing 10% fetal calf serum. Segments of mesenteric artery and thoracic aorta from 4-week-old SHR and age-matched WKY rats were similarly cultured. The NGF content in conditioned medium was measured using an enzyme immunoassay. The protein content of VSMC was measured by the Lowry method. RESULTS: Total NGF content in the cell culture medium was increased during an exponential growth phase and then gradually decreased during a quiescent phase in both rat strains. There were no significant differences in the levels of NGF secreted from mesenteric artery and thoracic aorta segments between the SHR and WKY rats. The differences in cellular protein content between SHR and WKY rats were very small. CONCLUSIONS: In contrast to the reports of increased NGF in SHR tissues, our data demonstrate that NGF secretion was lower in VSMC from SHR, and was equivalent in mesenteric artery and thoracic aorta segments from SHR and WKY rats. We have no clear explanation for these observations, but the present results indicate that upregulation of NGF in SHR tissues is not responsible for a simple enhancement of NGF synthesis in VSMC, and suggest a breakdown of the regulatory mechanism or mechanisms of NGF gene expression in SHR tissues.

Animals↗
PubMed1992

Increased nerve growth factor levels in spontaneously hypertensive rats.

OBJECTIVE: Increased sympathetic innervation has been reported in spontaneously hypertensive rats (SHR); however, the precise mechanisms involved are not yet clear. Nerve growth factor (NGF), a neurotrophic peptide in peripheral sympathetic neurons, is believed to contribute to this phenomenon. METHODS: We measured the content of NGF in SHR and control Wistar-Kyoto (WKY) rats during development. Mesenteric artery, spleen, heart and sciatic nerve were isolated and homogenized. NGF content in the supernatant fractions was measured using a highly sensitive and specific two-site enzyme immunoassay. RESULTS: At 3 weeks of age, SHR had a greater NGF content in the spleen, the sciatic nerve and the mesenteric artery than WKY rats. However, these differences disappeared completely at 12 weeks of age. Cardiac NGF content was slightly lower in 3-week-old SHR and, conversely, higher in 12-week-old SHR than in age-matched WKY rats. CONCLUSIONS: These findings suggest that, except for the heart, the SHR tissues observed overproduce NGF at a young age, leading to enhancement of peripheral sympathetic nervous system activity and the production of vasoconstrictive catecholamines.

Aging↗
PubMed1991

New role of nerve growth factor--an inhibitory neuromodulator of adrenergic transmission.

In the present study, we investigated the effects of nerve growth factor (NGF) on norepinephrine (NE) release from peripheral sympathetic nerve endings of rat mesenteric artery. We made isolated mesenteric artery-intestinal loop preparations, by the modified method of Castelluci et al., from 4- and 8-week-old Wistar rats. NGF produced a dose-dependent inhibition of NE overflow from sympathetic nerve endings evoked by electrical nerve stimulation in the range of 0.1-10 ng/ml. Inhibition of NE overflow also occurred in the presence of a neuronal uptake blocker, desipramine (5 x 10(-8) M). NGF showed no effect on pressor response to exogenous NE (1 micrograms). These results suggest that NGF inhibits NE release from sympathetic nerve endings, in other words, NGF acts as an inhibitory neuromodulator of adrenergic transmission. This function of NGF might be considered as an inhibitory feedback mechanism against catecholamine-stimulated NGF synthesis.

Animals↗
PubMed1991

Release of nerve growth factor from cultured aortic smooth-muscle cells.

Conditioned medium from cultured aortic smooth-muscle cells from rat aorta yielded neurite-extending effects on sensory and sympathetic ganglia of chick embryos. These effects were blocked by adding specific antiserum against 2.5S nerve growth factor (NGF), suggesting that NGF might be released from vascular smooth-muscle cells.

Animals↗
PubMed1991

Antihypertensive effects of oral calcium supplementation in spontaneously hypertensive rats.

This study was designed to clarify the mechanisms underlying the antihypertensive action of oral calcium supplementation in SHR. Four-week-old SHR and age-matched WKY were divided into calcium-supplemented and control groups. Calcium supplementation was carried out by giving 1.2% CaCl2 solution as drinking water ad libitum. Distilled water was given to the control group. After 3 weeks of treatment, plasma NE, pressor response to NE in isolated mesenteric artery, platelet cytosolic free calcium concentration and membrane fluidity of erythrocytes were evaluated. The elevation of blood pressure were retarded in calcium supplemented SHR. Calcium supplementation reduced the augmented pressor response to NE and the high level of cytosolic free calcium concentration in SHR. WKY showed no significant changes of these parameters by calcium supplementation. In conclusion, calcium supplementation reduces blood pressure through the reduction of sympathetic and vascular tone in SHR.

Administration, Oral↗
PubMed1991

Altered renin release from isolated superfused rat glomeruli in DOCA-salt hypertensive rats.

The present study was designed to clarify the role of calcium in suppressed renin release in DOCA-salt hypertension. Rat glomeruli were isolated by the modified Beierwaltes' sieving method. The glomeruli were superfused with Krebs-Ringer solution. Basal levels of renin release were lower in the DOCA-salt hypertensive rats (1.16 +/- 0.27 ng/ATI/hr/hr/10(4) glomeruli, mean +/- SEM, n = 8) than in the control rats (1.92 +/- 0.18, p less than 0.01, n = 8). Perfusion with a calcium free solution containing EGTA and A23187 stimulated renin release in the DOCA-salt hypertensive and control rats. The maximum levels of renin release during the perfusion in DOCA-salt hypertensive rats (1.79 +/- 0.17, n = 8) were lower than those in control rats (10.60 +/- 1.85, p less than 0.01, n = 8). These results suggest that high levels of intracellular calcium might not contribute to the suppression of renin release in DOCA-salt hypertension.

Animals↗
PubMed1991

[Effects of calcium antagonist, angiotensin-converting enzyme inhibitors and beta-blocker on hemodynamic and sympathetic nerve responses to exercise in essential hypertension].

To investigate the effects of antihypertensive drugs on hemodynamic and sympathetic nerve responses to exercise, graded ergometer exercise tests were performed before and after two-week administration of nifedipine, captopril and metoprolol in 18 patients with essential hypertension. The arterial pressure, heart rates (HR), and left ventricular functions as obtained by echocardiography, and the plasma norepinephrine (PNE) levels, were evaluated at rest and during submaximal exercise before and after two-week treatment with nifedipine (40 mg/day, 5 cases), captopril (37.5-75 mg/day, 6 cases) and metoprolol (60 mg/day, 7 cases). These 3 drugs significantly reduced systolic (SBP) and diastolic (DBP) blood pressures but caused no significant changes in resting PNE levels. Nifedipine produced no significant changes in HR and cardiac output (CO) at rest, but augmented the increase in HR (delta HR) and SBP (delta SBP) during submaximal exercise. The increase in PNE (delta PNE) was also augmented by nifedipine. Captopril reduced left ventricular end-diastolic volume and CO without changes in HR and fractional shortening (FS) at rest; whereas, it did not affect delta HR, delta CO, delta SBP or delta PNE during exercise. Metoprolol reduced HR and CO at rest, and also resulted in a decrease in delta FS and delta CO during submaximal exercise. delta SBP was unchanged and delta PNE was increased by treatment with metoprolol. These results indicate that, in hypertensive subjects, the effects on the hemodynamic and sympathetic nerve responses to exercise are different among these 3 antihypertensive drugs despite their identical effects on blood pressure.

Adrenergic beta-Antagonists↗
PubMed1991

[A case report of Creutzfeldt-Jakob disease associated with myocarditis].

We have encountered a case of Creutzfeldt-Jakob disease associated with myocarditis. A 77 year-old woman was admitted to a hospital with complaints of rapidly progressive visual disturbance, myoclonus and dementia. Electroencephalogram revealed a periodic synchronous discharge and Creutzfeldt-Jakob disease was suspected. Then she moved to our hospital, because acute myocarditis was combined with ST-T changes on electrocardiogram, and generalized hypokinetic motion of the left ventricle on echocardiogram. The abnormal findings in electrocardiography and echocardiography were transient. Blood levels of enzymes derived from the myocardium were slightly elevated. We could not find a distinct increase in the titer of neutralizing antibody to various viruses. In this case, the cause of myocarditis may have been associated with the infectious agent of Creutzfeldt-Jakob disease. This report might be the first one with a case of Creutzfeldt-Jakob disease complicated with myocarditis.

Aged↗
PubMed1990

Enhanced DNA synthesis of cultured vascular smooth muscle cells from spontaneously hypertensive rats. Difference of response to growth factor, intracellular free calcium concentration and DNA synthesizing cell cycle.

It is widely reported that cultured vascular smooth muscle cells (CVSMCs) from spontaneously hypertensive rats (SHR) show enhanced proliferation compared with cells from Wistar-Kyoto rats (WKY). The present studies were designed to find out whether this exaggerated proliferation in SHR is determined genetically and, if so, to evaluate the mechanism on the cell cycle. (1) Incorporation of [3H]thymidine into DNA was enhanced in CVSMCs from 3- and 12-week-old SHR compared with WKY but not in CVSMCs from DOCA-salt hypertensive rats compared with the cells from sham-operated rats. (2) DNA synthesis in SHR cells was enhanced further by addition of insulin (which is considered to be a progression factor) but not by arginine-vasopressin (AVP; considered to be a competence factor) or by angiotensin II (AII). On the other hand, insulin, AVP and AII significantly augmented DNA synthesis in WKY cells. (3) Intracellular free calcium concentration was slightly, but significantly, higher in SHR cells. (4) An increase in the population of DNA-synthesizing S-phase cells and decrease in (G2 + M)-phase cells in SHR were observed by flowcytometry. These data suggest (1) that enhanced DNA synthesis in CVSMCs from SHR is determined genetically, (2) that enhanced DNA synthesis in CVSMCs from SHR is largely dependent on an increased proportion of S-phase cells and (3) that this increase in S-phase cells in CVSMCs from SHR could be due to enhanced competence gene expression in SHR cells. (4) The increased intracellular free calcium concentration is compatible with an activation of the inositol-trisphosphate pathway.

Angiotensin II↗
PubMed1990

Effect of centrifugal force and catecholamines on glycosaminoglycans synthesis of vascular smooth muscle cells in culture.

To evaluate the effect of hypertension on glycosaminoglycan (GAG) synthesis, cultured vascular smooth muscle cells (CVSMCs) from the aorta of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were exposed to centrifugal forces and catecholamines. GAG synthesis of CVSMCs was measured by the incorporation of [3H]glucosamine into GAGs which were secreted into the culture medium for 24 h. Basal level of GAG synthesis was much higher in SHR than in WKY, when expressed in terms of DNA contents. When exposed to centrifugal force, CVSMCs from rats of both strains synthesized more GAGs. GAG synthesis was enhanced by both noradrenaline (NA) and adrenaline (Ad) in WKY. The enhanced GAG synthesis in WKY by NA or Ad was prevented by pretreatment with propranolol, but not prazosin. In SHR, NA and Ad did not enhance GAG synthesis at this concentration of catecholamines. However, the effects of propranolol or prazosin on GAG synthesis in SHR, when incubated with either NA or Ad, were compatible with the phenomena observed in WKY. Adding dibutyryl cyclic AMP to the culture medium enhanced GAG synthesis in rats of both strains. These data suggest that not only the mechanical stress of high intra-arterial pressure but also beta receptor stimulation, via increasing cyclic AMP, enhance GAG synthesis of vascular smooth muscle cells in hypertension.

Animals↗
PubMed1990

Contribution of calmodulin and protein kinase C to renin release in spontaneously hypertensive rats.

This study was designed to evaluate the contribution of calmodulin and protein kinase C to renin release from isolated glomeruli of spontaneously hypertensive rats (SHR, Okamoto and Aoki). Male 7-week-old SHR and age-matched control Wistar-Kyoto rats (WKY) were used in this study. Isolated glomeruli were sealed in the superfusion chamber and perfused with Krebs-Ringer solution at a constant flow of 0.3 mL/min. Renin release was increased by calmodulin inhibitor, W-7, and protein kinase C inhibitor, H-7, in both SHR and WKY. SHR showed higher maximal levels of renin release by W-7 and lower maximal levels by H-7 compared to WKY. These results indicate that calmodulin and protein kinase C play inhibitory roles in renin release from juxtaglomerular cells. The calmodulin-mediated suppression mechanism in renin release appears to be augmented in the SHR, whereas the protein kinase C-mediated system is attenuated.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Responses of cytosolic free calcium to ADP in platelets of spontaneously hypertensive rats.

Abnormalities of Ca2+ handling have been reported in patients with essential hypertension and in spontaneously hypertensive rats (SHR). In this study, responses of cytosolic Ca2+ to ADP in platelets of SHR were examined. Four- and seven-week-old male SHR and age- and sex-matched Wistar-Kyoto rats (WKY) were used. Basal levels of the intracellular Ca2+ concentration in platelets and responses to ADP were estimated using fluorescent indicator fura-2 in the medium containing 1 mmol/L CaCl2 and Ca2(+)-free buffer with 1 mmol/L EGTA. Basal levels of platelet cytosolic Ca2+ of SHR were significantly higher than those of WKY at 4 and 7 weeks of age in the presence of external Ca2+. However, no significant difference was observed in basal levels of platelet cytosolic Ca2+ in the Ca2(+)-free EGTA-containing buffer between SHR and WKY. The peak cytosolic Ca2+ concentration evoked by ADP was significantly diminished in SHR compared with WKY in the absence of external Ca2+, whereas the responses of platelet cytosolic Ca2+ to ADP were similar in SHR and WKY in the presence of external Ca2+. These results suggest that release from intracellular Ca2+ store is reduced in SHR and that the regulation of cytosolic Ca2+ in SHR is more dependent on extracellular Ca2+ compared with WKY.

Animals↗
PubMed1990

Platelet noradrenaline content as an integrated measure of variations in plasma noradrenaline.

To determine whether or not platelet noradrenaline (NA) content reflects a long-term variation of plasma NA concentration, the following experiments were carried out. During a 2-hour intravenous infusion of NA in rabbits, plasma NA concentration increased rapidly to an almost consistent level 1 h later, but platelet NA content increased linearly. One hour after the infusion, the plasma NA concentration returned to normal level, while platelet NA content decreased little and only returned to the original level about 80 h later. By the 24-hour cold exposure stimulation (4 +/- 0.5 degrees C), platelet NA content and urinary NA excretion increased significantly in rats. There was a significant correlation between the urinary NA excretion and platelet NA content. In a patient with pheochromocytoma, the high plasma NA concentration returned to nearly normal levels a few hours after removal of the tumor, platelet NA content returned to normal levels 4 days after surgery. These results indicate that the measurement of platelet NA content serves as a better index for obtaining an average variation of NA concentration and sympathetic nerve activity. The measurement of platelet NA content also provides a reliable means of diagnosing pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1989

Norepinephrine overflow and re-uptake in perfused mesenteric arteries of Dahl salt-sensitive and salt-resistant rats.

We compared the overflow of endogenous norepinephrine (NE) upon electrical stimulation, the associated pressor response and rate of initial neuronal uptake of 3H-I-NE in the perfused mesenteric arteries of Dahl salt-sensitive (DS) and salt-resistant (DR) rats on two dietary NaCl regimens (0.4 and 8.0% for 2 weeks) from 4 weeks of age. The tissues of two rats, a DS and a DR control, were simultaneously processed and subjected to the same electrical stimulation. The pressor response and overflow of endogenous NE during periarterial nerve stimulation (5, 10 Hz, 1 min) in the tissue of DS rats on a high-salt diet (HS) were significantly greater, while those of DS on a low-salt diet (LS) were moderately but significantly higher than those of DR rats on either a high (HR) or a low-salt diet (LR). The tissue content of NE in DS rats was significantly lower than DR groups. There was a significantly reduced 3H-I-NE uptake in the tissues of DS rats on both salt diet groups compared with DR rats. A submaximal dose of exogenous NE evoked a significantly greater pressor response amplitude in mesenteric tissues from DS rats on a high-salt diet than in any of the other three groups, suggesting that smooth muscle supersensitivity, either in the density of the NE receptor or in the excitation-contraction coupling system, had been induced in the vasculature of DS rats by feeding them on a high-salt diet for 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Norepinephrine release and reuptake by hypothalamic synaptosomes of spontaneously hypertensive rats.

We compared the overflow of endogenous norepinephrine during electrical field stimulation, the norepinephrine content, and the rate of initial neuronal uptake of [3H]norepinephrine in synaptosomes isolated from hypothalamus and brainstem of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at 7 and 13 weeks of age. The synaptosomes of two rats, a SHR and a WKY rat control, were simultaneously processed and subjected to the same electrical field stimulation. The overflow of endogenous norepinephrine during electrical stimulation (2 Hz, 2 minutes) in the hypothalamic synaptosomes of 7-week-old SHR was significantly greater, whereas the overflow of 13-week-old SHR was equivalent to the age-matched WKY rat. The norepinephrine content of synaptosomes was about the same in SHR and age-matched controls. There was also significantly enhanced [3H]norepinephrine uptake in the hypothalamic synaptosomes of young SHR, but neither the hypothalamic nor the brainstem samples of 13-week-old SHR showed any significant difference in their rate of [3H]norepinephrine uptake. These data are similar to those we observed (unpublished observations) in perfused mesenteric artery system in which norepinephrine release was significantly elevated during periarterial nerve stimulation only in young SHR. Thus, these results suggest that a parallel enhancement of norepinephrine release in hypothalamus with that of peripheral nervous system may play an important role during development of hypertension in young SHR.

Aging↗
PubMed1989

Norepinephrine overflow in perfused mesenteric arteries of spontaneously hypertensive rats.

We examined the overflow of endogenous norepinephrine with electrical stimulation, the associated pressor response, and rate of initial neuronal uptake of [3H]norepinephrine in perfused mesenteric arteries of 7- and 13-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The tissues of two rats, a spontaneously hypertensive and a WKY control rat, were simultaneously processed and subjected to the same electrical stimulation. Both absolute and fractional overflow of endogenous norepinephrine during periarterial nerve stimulation (5 and 10 Hz for 1 minute) in the tissue of 7-week-old SHR was significantly greater whereas overflow of 13-week-old SHR was equivalent as compared with that of the age-matched WKY rats. The tissue content of norepinephrine was 20-25% higher in SHR of both ages. There was significantly enhanced [3H]norepinephrine uptake in the tissues of young SHR, but no difference was observed in the older SHR. The pressor response to periarterial nerve stimulation was significantly enhanced in 7-week-old SHR and much more so at the older age as compared with the WKY control rats. Exogenous norepinephrine dose-response curves in the tissues of 7-week-old SHR exhibited a parallel leftward shift, characteristic of a change in sensitivity, whereas that of 13-week-old SHR showed a much steeper slope as compared with the respective WKY control rats. This finding suggests that in addition to smooth muscle supersensitivity, structural alterations had occurred in vasculature of 13-week-old SHR. These data indicate that in SHR both the exocytotic release of norepinephrine and the responsiveness of the vascular smooth muscle cells are enhanced in the developmental stage of hypertension whereas smooth muscle supersensitivity to norepinephrine and nonspecific structural alterations primarily contribute to the maintenance of hypertension at 13 weeks of age.

Animals↗