Biomedical subjects

Katsuo Kamata

Publications and source records attributed to Katsuo Kamata.

43 records · Page 3Linked to original sources

PubMed2003

[Possible involvement of IGF-1 receptor and IGF-binding protein in insulin-induced enhancement of noradrenaline response in diabetic rat aorta].

The aim of the present study was to investigate the link between the changes in vascular responsiveness associated with hyperinsulinemia in established STZ-induced diabetes and the growth factors signal system. We have shown that in rats with established diabetes, high-insulin treatment can enhances NA-induced contractility. This enhancement probably results from an upregulation of the expression of the mRNA for the alpha 1B- or alpha 1D-adrenergic receptor that is secondary to the hyperinsulinemia. The above effects may be made possible as a result of the increase in IGF-1 receptors and the decreased IGFBPs expressions that occur in the aorta in long-term insulin deficiency. In contrast, those insulin treatments can normalise the impaired endothelium-dependent relaxation, probably by inducing an overexpression of eNOS and VEGF. Furthermore, the expression of the IGF-1 receptor was higher in the aorta in insulin-treated diabetic than in untreated diabetes. This presumably increased the expression of VEGF mRNA, and the increased VEGF presumably upregulated eNOS, thereby resulting in an amelioration in the endothelial dysfunction otherwise seen in diabetic rats. The downside is that such a perturbation of the activity in the IGF-1 system in diabetes could be a key event in the progress of arteriosclerosis and hypertension in syndromes involving hyperinsulinemia.

Animals↗

PubMed2002

Modulation by hydrogen peroxide of noradrenaline-induced contraction in aorta from streptozotocin-induced diabetic rat.

Hydrogen peroxide (H(2)O(2)) is known to modify vascular tone in various preparations and its production is elevated in the diabetic aorta. We have investigated its possible involvement in regulation of the noradrenaline-induced contractile response in aorta from streptozotocin-induced diabetic rats. In diabetic but not in control aorta, the noradrenaline-induced contraction was significantly enhanced by catalase and significantly inhibited by polyethylene-glycolated superoxide dismutase. Adding catalase to the superoxide dismutase prevented the latter's attenuation of the contraction. In the presence of N(G)-nitro-L-arginine, the noradrenaline-induced contraction of aorta from diabetic rats, but not from controls, was inhibited by catalase treatment. Noradrenaline increased the nitrite and nitrate levels in the perfusates from control and diabetic aortic strips. In the latter, the noradrenaline-induced nitrite and nitrate level was significantly enhanced by incubation with superoxide dismutase but not by incubation with catalase plus superoxide dismutase. Thus, endogenously produced H(2)O(2) may be an important factor in the regulation of aortic tone in diabetic rats. Enhanced production of H(2)O(2) in the aorta from diabetic rats may seem contribute to the endothelial generation of nitric oxide and vasoconstrictor prostanoids.

Acetylcholine↗

PubMed2002

Mechanism underlying gamma-aminobutyric acid-induced antihypertensive effect in spontaneously hypertensive rats.

We examined the effects of gamma-aminobutyric acid (GABA) on the blood pressure in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. A single oral administration (0.5 mg/kg) significantly lowered the systolic blood pressure in spontaneously hypertensive rats, but not in normotensive rats. In the mesenteric arterial bed, the perivascular nerve stimulation-induced increase in perfusion pressure and noradrenaline release were significantly inhibited by GABA in spontaneously hypertensive rats, but not in normotensive rats, and attenuated by the selective GABA(B) receptor agonist, baclofen, but not by the selective GABA(A) receptor agonist muscimol. The inhibitory effects of GABA on the perivascular nerve stimulation-induced increase in perfusion pressure and noradrenaline release were completely antagonized by the selective GABA(B) receptor antagonist, saclofen, but not by the selective GABA(A) receptor antagonist, bicuculline. These results suggest that, in spontaneously hypertensive rats, GABA has an antihypertensive effect due to its inhibition of noradrenaline release from sympathetic nerves in the mesenteric arterial bed via presynaptic GABA(B) receptors.

Animals↗

PubMed2002

Lysophosphatidylcholine potentiates vascular contractile responses in rat aorta via activation of tyrosine kinase.

We previously reported that while lysophosphatidylcholine (LPC) does not itself produce contraction, it significantly potentiates the contractile responses induced by high-K(+), UK14,304 (a selective alpha(2)-adrenoceptor agonist) and phorbol ester in the endothelium-denuded rat aorta. To further investigate this phenomenon, we examined the effects of genistein and tyrphostin B42 (both tyrosine kinase inhibitors) on the LPC-induced potentiation of the contractile responses to high-K(+) and UK14,304 in the endothelium-denuded rat aorta. Although genistein (3 x 10(-6) M, 10(-5) M) did not affect the high-K(+)-induced contractile response, it selectively inhibited the potentiating effect of LPC on the contraction and it strongly inhibited the LPC-induced augmentation of the associated increases in [Ca(2+)](i). Genistein also attenuated the LPC-induced augmentation effects on both the increase in [Ca(2+)](i) and contractile response induced by the UK14,304. In contrast, daidzein (10(-5) M) did not inhibit the potentiating effect of LPC. Tyrphostin B42 (3 x 10(-5) M) attenuated the potentiating effect of LPC on high K(+)-induced contractions. Western blot analysis showed that LPC increased the tyrosine phosphorylation of a number of proteins, including 42 and 44 kDa proteins and 53 - 64 kDa proteins. These protein phosphorylations were inhibited by genistein. Sodium orthovanadate (10(-4) M), a tyrosine phosphatase inhibitor, also markedly enhanced the high-K(+)-induced contractile responses. This enhancing effect was attenuated by genistein. These results suggest that the LPC-induced augmentation of contractile responses in the rat aorta is due to activation of tyrosine kinase, which in turn regulates Ca(2+) influx.

Adrenergic alpha-Agonists↗

PubMed2002

Effects of chronic administration of the novel endothelin antagonist J-104132 on endothelial dysfunction in streptozotocin-induced diabetic rat.

1. The biosynthesis of endothelin-1 is increased in the diabetic state. So this peptide may cause diabetic vascular complications. We tested this possibility by chronically administering J-104132, a potent orally active mixed antagonist of endothelin A and B (ET(A)/ET(B)) receptors to streptozotocin (STZ)-induced diabetic rats and focusing on changes in endothelial function. 2. The acetylcholine (ACh)-induced endothelium-dependent relaxation was impaired in diabetic rats and this impairment was significantly attenuated following chronic administration of J-104132 (10 mg kg(-1), p.o., daily for 4 weeks). 3. In an in vitro experiment using aortae from diabetic rats, the ACh-induced relaxation was not changed by the presence of J-104132 (3 x 10(-9) M). 4. The expression levels of the mRNA for endothelial nitric oxide synthase was comparable among aortae from the three groups (control, diabetic and chronically J-104132-treated diabetic). 5. The amount of superoxide anion was significantly greater in aortae from diabetic rats than in controls. Chronic J-104132 treatment significantly decreased the level of superoxide anion in diabetic rats. 6. The expression of the p22phox mRNA for the NADH/NADPH oxidase subunit was significantly increased in STZ-induced diabetic rats and this increase was completely prevented by chronic administration of J-104132. 7. These results suggest that in STZ-induced diabetic rats, ET-1 may be directly involved in impairing endothelium-dependent relaxation via increased superoxide-anion production.

Acetylcholine↗

PubMed2002

Short-term insulin treatment and aortic expressions of IGF-1 receptor and VEGF mRNA in diabetic rats.

We investigated the relationship between the changes in vascular responsiveness and growth factor mRNA expressions induced by 1-wk treatment with high-dose insulin in control and established streptozotocin (STZ)-induced diabetes. Aortas from diabetic rats, but not those from insulin-treated diabetic rats, showed impaired endothelium-dependent relaxation in response to ACh (vs. untreated controls). The ACh-induced nitrite plus nitrate (NOx) level showed no significant difference between controls and diabetics. Insulin treatment increased NOx only in diabetics. In diabetics, insulin treatment significantly increased the aortic expressions of endothelial nitric oxide synthase (eNOS) mRNA and VEGF mRNA. The expression of IGF-1 mRNA was unaffected by diabetes or by insulin treatment. In contrast, the mRNA for the aortic IGF-1 receptor was increased in diabetics and further increased in insulin-treated diabetics. In aortic strips from age-matched control rats, IGF-1 caused a concentration-dependent relaxation. This relaxation was significantly stronger in strips from STZ-induced diabetic rats. These results suggest that in STZ-diabetic rats, short-term insulin treatment can ameliorate endothelial dysfunction by inducing overexpression of eNOS and/or VEGF mRNAs possibly via IGF-1 receptors. These receptors were increased in diabetes, perhaps as result of insulin deficiency.

Acetylcholine↗

PubMed2002

Effects of chronic administration of L-arginine on vasoactive responses induced by endothelin-1 and its plasma level in streptozotocin-induced diabetic rats.

To investigate the mechanism underlying increased endothelin-1 (ET-1) release in diabetic rats, we administered L-arginine chronically to streptozotocin (STZ)-induced diabetic rats. The plasma concentrations of glucose, ET-1 and NOx (NO2- + NO3-) were all significantly raised at 10 weeks after the STZ injection. Chronic administration of L-arginine resulted in a significantly higher plasma NOx concentration and a significantly lower plasma ET-1 level at 10 weeks compared with the untreated diabetic group. ET-1 induced a biphasic vasodilator/vasoconstrictor response in the perfused isolated mesenteric arterial beds from all groups. The vasodilatation was significantly greater in diabetic rats than in age-matched controls. Chronic oral L-arginine administration had no significant effect on the enhanced ET-1-induced vasodilatation seen in the untreated diabetic rats. The vasoconstrictions induced by ET-1 and methoxamine were significantly attenuated in STZ-diabetic rats. The attenuated vasoconstrictor response to ET-1, but not that to methoxamine, was further attenuated by chronic treatment with L-arginine. We conclude that since chronic L-arginine administration not only reduced the increase in plasma ET-1 levels but also further attenuated the ET-1-induced vasoconstriction without affecting the change in vasodilatation, chronic L-arginine administration could be valuable for the treatment of the symptoms of diabetic mellitus related to ET-1.

Animals↗