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Life Sciences | 1992

Functional changes in vascular smooth muscle and endothelium of arteries during diabetes mellitus

Katsuo Kamata; Noriyuki Miyata; Toichi Abiru; Yutaka Kasuya

To investigate the influence of diabetes mellitus on the responsiveness of the vascular smooth muscle, the effects of various vasoactive agents on the reactivity of the vascular smooth muscle from diabetic animals have been undertaken, focusing on the functional changes in the endothelium, alpha-adrenoceptors, beta-adrenoceptors, voltage-dependent Ca(2+)-channels, receptor-operated Ca(2+)-channels, phosphatidylinositol turnover and potassium channels. Among the functional changes, it is a common phenomenon that decreases in acetylcholine-induced production of cyclic GMP are due to the attenuation of release of endothelium-derived relaxing factor through an impairment of endothelium; this observation was found in both rats and rabbits with diabetes mellitus. These functional changes in diabetes may be responsible for the vascular complications such as coronary heart disease, cerebrovascular disease, and an acceleration in atherosclerosis.


Life Sciences | 1993

Changes in endothelium-dependent relaxation and levels of cyclic nucleotides in the perfused mesenteric arterial bed from streptozotocin-induced diabetic rats

Toichi Abiru; Yohko Watanabe; Katsuo Kamata; Yutaka Kasuya

The influence of diabetes on the function of vascular endothelium was examined with respect to the role of nitric oxide (NO) in the regulation of blood pressure (BP) in vivo, the vascular relaxation, and levels of cAMP and cGMP in the effluent of the perfused mesenteric arterial bed from streptozotocin-induced diabetic rats. An intravenous injection of 100 mg/kg N omega-nitro-L-arginine methylester (L-NAME) caused hypertension in both diabetic rats and controls. However, the degree of hypertension in the diabetic rats was significantly lower than that in the controls. Acetylcholine (ACh)-induced vasorelaxation of the perfused mesenteric arterial bed decreased in diabetic rats. At the same time, the levels of cAMP and cGMP in the effluent of the diabetic rats were also lower than in the controls. These data indicate that NO formation is involved in the regulation of BP in rats, and is decreased in diabetic rats, due to an impairment of the vascular endothelium, including the endothelium of resistance vessels.


General Pharmacology-the Vascular System | 1995

Endothelium-derived hyperpolarizing factor does not contribute to the decrease in endothelium-dependent relaxation in the aorta of streptozotocin-induced diabetic rats

Kazuki Endo; Toichi Abiru; Haruhiko Machida; Yutaka Kasuya; Katsuo Kamata

1. We examined the contribution of endothelium-derived hyperpolarizing factor (EDHF) to the impairment of endothelium-dependent relaxation caused by acetylcholine (ACh) in the aorta of streptozotocin-induced diabetic rats, by using N omega-L-nitro-arginine methylester (L-NAME) and tetraethylammonium chloride (TEA) to inhibit nitric oxide (NO) and EDHF, respectively. 2. ACh-induced relaxation of the aorta decreased in diabetic rats. In contrast, sodium nitroprusside-induced relaxation was the same in diabetic rats and control rats. 3. Treatment with 5 x 10(-7) M L-NAME resulted in a right shift of the dose-response curves of ACh-induced relaxation in the aorta. The shift was greater in the control aorta. 4. Treatment with 5 x 10(-4) M TEA resulted in a similar right shift in both the control and diabetic aorta. 5. Therefore, while endothelium-derived NO appears to contribute to the impairment of ACh-induced endothelium-dependent relaxation in the aorta of diabetic rats, EDHF does not.


European Journal of Pharmacology | 1993

Simultaneous measurement of vasodilation and changes in cyclic nucleotides in the perfused mesenteric arterial bed of the rat

Toichi Abiru; Yohko Watanabe; Katsuo Kamata; Yutaka Kasuya

We examined the relationship between relaxation responses of the mesenteric arterial bed and the levels of cAMP and cGMP released from the rat mesenteric arterial bed. Perfusions of mesentery preparations with 1 microM acetylcholine, 0.1 microM calcium ionophore A23187, and 1 microM sodium nitroprusside all produced complete and long-lasting relaxation and increased the levels of cAMP as well as cGMP in the effluent. In endothelium-denuded preparations, acetylcholine did not elicit either vasorelaxation or an increase in cAMP and cGMP levels. Perfusion of the endothelium-denuded preparation with 1 microM sodium nitroprusside evoked complete relaxation and a marked increase in cGMP levels but not cAMP levels. Isoproterenol (1 microM) produced complete relaxation and an increase in cAMP levels, but did not affect cGMP levels either in the preparation with or in that without endothelium. Acetylcholine (0.001-1 microM) relaxed the preparation and increased cAMP and cGMP levels in the effluent in a dose-dependent manner. The acetylcholine-induced relaxation was reversed by 45% following perfusion with 10 microM methylene blue, and both the cAMP and cGMP levels were decreased. L-NG-Monomethyl arginine (L-NMMA) (100 microM), a nitric oxide synthase inhibitor, completely reversed the relaxation induced by 0.1 microM acetylcholine and reduced the elevated cGMP levels. Indomethacin (1 microM) reduced the acetylcholine-induced cAMP release, but did not alter the vasorelaxation in response to acetylcholine. We propose a novel method for the simultaneous measurement of vasodilation and changes in cAMP and cGMP levels released from the rat mesenteric arterial bed. We conclude that this method may provide information about the function of the endothelium of resistance vessels.


Archive | 1988

2-alkynyladenosines as antihypertensive agents

Tadashi Miyasaka; Akira Matsuda; Toichi Abiru; Haruhiko Machida


Canadian Journal of Physiology and Pharmacology | 1990

Differences in vascular responses to vasoactive agents of basilar artery and aorta from rabbits with alloxan-induced diabetes

Toichi Abiru; Katsuo Kamata; Noriyuki Miyata; Yutaka Kasuya


European Journal of Pharmacology | 1995

Differential vasodilatory action of 2-octynyladenosine (YT-146), an adenosine A2 receptor agonist, in the isolated rat femoral artery and vein

Toichi Abiru; Kazuki Endo; Haruhiko Machida


Archive | 1986

Antihypertensive agents comprising 2-alkynyladenosines as active ingredients

Tadashi Miyasaka; Akira Matsuda; Toichi Abiru; Haruhiko Machida


Life Sciences | 1998

Effects of nucleotides on learning and memory in a Morris water maze test in normal and basal forebrain-lesioned rats.

Shuichi Miyazaki; Masahiro Imaizumi; Toichi Abiru; Haruhiko Machida


Journal of pharmacobio-dynamics | 1991

Attenuation of Depressor Response Induced by Platelet Activating Factor and Acetylcholine in Streptozotocin-Induced Diabetic Rats

Toichi Abiru; Katsuo Kamata; Yutaka Kasuya

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Haruhiko Machida

National Institutes of Health

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Noriyuki Miyata

Taisho Pharmaceutical Co.

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